, Adult wild-type AB, Golden (see Note 3 and Note 4) and Tg(mpx::GFP) transgenic fish

, 5 mM Nacl, 0.17 mM KCl, 0.33 mM CaCl 2 , 0.33 mM MgSO 4 (from sterilized stock solutions) in sterilized water

. Stereomicroscope,

, Petri dishes 90x14 mm

, Very fine forceps, Tweezers #5 Dumont, Dumoxel/Biology Grade

, Burkholderia cenocepacia K56-2 and B. stabilis LMG1429, expressing a fluorescent reporter

, Luria Bertani (LB) broth: 10 g Bacto-tryptone, 5g yeast extract, 10 g NaCl. Add to 800mL H2O. Adjust pH to 7.5 with NaOH. For agar plates add 1.5% Bacto agar. Adjust volume to 1L with dH2O and sterilize by autoclaving (121 °C, 20 minutes)

. Chloramphenicol, 100 mg/mL stock solution in 100% ethanol (store at -20°C): For Burkholderia, we use Luria Broth (LB) medium with 100 mg/l of chloramphenicol, vol.11

, Phosphate-buffered saline (PBS) 1x

, Phenol red (PR) solution, 0.5%

. Microinjector, Femto Jet (Eppendorf)

, Mechanical xyz micromanipulator arm, p.152

, Micro loader pipette tips

, Borosilicate glass capillaries, vol.10

, Agarose plates (1-1.5 % agarose in E3 medium) for injection containing slots of 1 by 1 mm, vol.13

, Tricaine (MS222) 20x, 400 mg in 100 mL of sterile water, adjust pH 7.0 with Tris-HCl 1M pH9 (around 2.1 mL). Aliquot in 15 mL tubes and freeze at -20°C. After use, keep at 4°C

, LB 1.5% agar plates (See section 2.2 step 2) with appropriate antibiotics, vol.14

, LB 1.5% agar plates, square dishes 125/15mm (~50 mL per plate) with appropriate antibiotics, vol.15

, Pipette man and tips

/. Trypsin and . Edta,

, Triton X-100 2% in H 2 O

, Inverted fluorescence and fluorescence multizoom microscopes with camera and supplied imaging software, vol.16

, Glass-bottom dishes

, Microscope depression slides

, Tools for qRT-PCR and RNA-Seq analysis

, RNase-free work zone

, RNase-eliminating solution such as RNase Away

. Rnase,

D. Rnase and . Water,

. Trizol®,

7. Ethanol,

I. Dnase and R. Free,

, Photospectrometer to quantify RNA

, qPCR Primers with Tm of 60°C (see Note 48)

, Lightcycler 480 with software: Light Cycler, p.480

, well white plates with transparent sealing foils for Lightcycler 480 (Roche)

, SYBR Green mix adapted for your machine: For the LC480: Light Cycler 480 SYBR Green I Master (Roche)

P. Drevinek and E. Mahenthiralingam, Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence, Clin. Microbiol. Infect, vol.16, issue.7, pp.821-851, 2010.

M. Holden, H. Seth-smith, L. C. Crossman, M. Sebaihia, S. D. Bentley et al., The genome of Burkholderia cenocepacia J2315, an epidemic pathogen of cystic fibrosis patients, J. Bacteriol, vol.191, issue.1, pp.261-77, 2009.

J. J. Varga, L. Losada, A. M. Zelazny, M. Kim, J. Mccorrison et al., Draft Genome Sequences of Burkholderia cenocepacia ET12 Lineage Strains K56-2 and BC7, Genome Announc, vol.1, issue.5, 2013.

B. A. Abdulrahman, A. A. Khweek, A. Akhter, K. Caution, S. Kotrange et al., Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis, Autophagy, vol.7, pp.1359-1370, 2011.

S. Al-khodor, K. Marshall-batty, V. Nair, L. Ding, D. E. Greenberg et al., , 2014.

, Burkholderia cenocepacia J2315 escapes to the cytosol and actively subverts autophagy in human macrophages, Cell. Microbiol, vol.16, pp.378-395

V. Brinkmann and A. Zychlinsky, Neutrophil extracellular traps: is immunity the second function of chromatin?, J. Cell Biol, vol.198, pp.773-783, 2012.

E. M. Bruscia, P. Zhang, E. Ferreira, C. Caputo, J. W. Emerson et al., Macrophages directly contribute to the exaggerated inflammatory response in cystic fibrosis transmembrane conductance regulator-/-mice, Am. J. Respir. Cell Mol. Biol, vol.40, pp.295-304, 2009.

J. Bylund, P. A. Campsall, R. C. Ma, B. D. Conway, and D. P. Speert, Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease, J. Immunol, vol.174, pp.3562-3569, 2005.

C. J. Cambier, K. K. Takaki, R. P. Larson, R. E. Hernandez, D. M. Tobin et al., Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids, Nature, vol.505, pp.218-222, 2014.

C. H. Chiu, S. Wong, R. E. Hancock, and D. P. Speert, Adherence of Burkholderia cepacia to respiratory tract epithelial cells and inhibition with dextrans, Microbiology, vol.147, pp.2651-2658, 2001.

H. Clay, J. M. Davis, D. Beery, A. Huttenlocher, S. E. Lyons et al., , 2007.

, Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish

, Cell Host Microbe, vol.2, pp.29-39

E. Colucci-guyon, J. Tinevez, S. Renshaw, and P. Herbomel, Strategies of professional phagocytes in vivo: unlike macrophages, neutrophils engulf only surface-associated microbes, J. Cell Sci, pp.3053-3059, 2011.
URL : https://hal.archives-ouvertes.fr/pasteur-02616471

M. R. Cronan and D. M. Tobin, Fit for consumption: zebrafish as a model for tuberculosis, Dis. Model. Mech, vol.7, pp.777-784, 2014.

S. Curado, D. Y. Stainier, A. , and R. M. , Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies, Nat. Protoc, vol.3, pp.948-954, 2008.

M. C. Dinauer, M. A. Gifford, N. Pech, L. L. Li, and P. Emshwiller, Variable correction of host defence following gene transfer and bone marrow transplantation in murine X-linked chronic granulomatous disease, Blood, vol.97, pp.3738-3745, 2001.

P. Drevinek and E. Mahenthiralingam, Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence, Clin. Microbiol. Infect, vol.16, pp.821-830, 2010.

F. Ellett and G. J. Lieschke, Computational quantification of fluorescent leukocyte numbers in zebrafish embryos, Methods Enzymol, vol.506, pp.425-435, 2012.

R. S. Flannagan and M. Valvano, Burkholderia cenocepacia requires RpoE for growth under stress conditions and delay of phagolysosomal fusion in macrophages, Microbiology, vol.154, pp.643-653, 2008.

R. S. Flannagan, V. Jaumouillé, K. K. Huynh, J. D. Plumb, G. P. Downey et al., Burkholderia cenocepacia disrupts host cell actin cytoskeleton by inactivating Rac and Cdc42, Cell. Microbiol, vol.14, pp.239-254, 2012.

T. A. Fuchs, U. Abed, C. Goosmann, R. Hurwitz, I. Schulze et al., Novel cell death program leads to neutrophil extracellular traps, J Cell Biol, vol.176, pp.231-272, 2007.

S. Ganesan and U. S. Sajjan, Host Evasion by Burkholderia cenocepacia, Front. Cell. Infect, 2011.

. Microbiol, , p.25

M. Gavrilin, D. H. Abdelaziz, M. Mostafa, B. Abdulrahman, J. Grandhi et al., Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia, J. Immunol, vol.188, pp.3469-3477, 2012.

L. Guyader, D. Redd, M. J. Colucci-guyon, E. Murayama, E. Kissa et al., Origins and unconventional behaviour of neutrophils in developing zebrafish, Blood, vol.111, pp.132-141, 2008.

A. Hanuszkiewicz, P. Pittock, F. Humphries, H. Moll, A. R. Rosales et al., Identification of the flagellin glycosylation system in Burkholderia cenocepacia and the contribution of glycosylated flagellin to evasion of human innate immune responses, J. Biol. Chem, vol.289, issue.27, pp.19231-19275, 2014.

D. Hartl, A. Gaggar, E. Bruscia, A. Hector, V. Marcos et al., Innate immunity in cystic fibrosis lung disease, J. Cyst. Fibros, vol.11, pp.363-382, 2012.

C. Hubeau, M. Lorenzato, J. P. Couetil, D. Hubert, D. Dusser et al., , 2001.

, Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa, Clin. Exp

, Immunol, vol.124, pp.69-76

J. Hughes, J. Stewart, G. Barclay, and J. Govan, Priming of neutrophil respiratory burst activity by lipopolysaccharide from Burkholderia cepacia, Infect. Immun, vol.65, pp.4281-4287, 1997.

S. K. Kaza, S. Mcclean, and M. Callaghan, IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteria, Int. J. Med. Microbiol, vol.301, pp.26-33, 2011.

B. T. Kopp, B. Abdulrahman, . Khweek, S. B. Kumar, A. Akhter et al., Exaggerated inflammatory responses mediated by Burkholderia cenocepacia in human macrophages derived from Cystic fibrosis patients, Biochem, 2012.

, Biophys. Res. Commun, vol.424, pp.221-227

K. E. Maloney and M. A. Valvano, The mgtC gene of Burkholderia cenocepacia is required for growth under magnesium limitation conditions and intracellular survival in macrophages, 2006.

. Immun, , vol.74, pp.5477-5486

J. Mesureur and A. C. Vergunst, Zebrafish embryos as a model to study bacterial virulence, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02381118

, Methods Mol. Biol, vol.1197, pp.41-66

S. Mostowy, L. Boucontet, M. J. Mazon-moya, A. Sirianni, P. Boudinot et al., The zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy, PLoS Pathog, vol.9, 2013.
URL : https://hal.archives-ouvertes.fr/hal-02650798

K. Pohl, E. Hayes, J. Keenan, M. Henry, P. Meleady et al., A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy, Blood, vol.124, pp.999-1009, 2014.

L. A. Porter and J. B. Goldberg, Influence of neutrophil defects on Burkholderia cepacia complex pathogenesis, Front. Cell. Infect. Microbiol, vol.1, p.152, 2011.

T. K. Prajsnar, V. T. Cunliffe, S. J. Foster, and S. A. Renshaw, A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens, Cell. Microbiol, vol.10, pp.2312-2325, 2008.

L. S. Saini, S. B. Galsworthy, M. John, and M. Valvano, , 1999.

U. Sajjan, G. Thanassoulis, V. Cherapanov, A. Lu, C. Sjolin et al., Enhanced susceptibility to pulmonary infection with, Burkholderia cepacia in Cftr, vol.69, pp.5138-5150, 2001.

U. Sajjan, M. Corey, A. Humar, E. Tullis, E. Cutz et al., Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients, J Med Microbiol, vol.50, pp.535-546, 2001.

M. S. Saldías and M. A. Valvano, Interactions of Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria with epithelial and phagocytic cells, Microbiology, vol.155, pp.2809-2817, 2009.

U. Schwab, L. H. Abdullah, O. S. Perlmutt, D. Albert, C. W. Davis et al.,

P. Gilligan, H. Neubauer, and S. H. Randell, Localization of Burkholderia cepacia complex bacteria in cystic fibrosis lungs and interactions with Pseudomonas aeruginosa in hypoxic mucus, Infect. Immun, vol.82, pp.4729-4745, 2014.

S. A. Sousa, M. Ulrich, A. Bragonzi, M. Burke, D. Worlitzsch et al., Virulence of Burkholderia cepacia complex strains in gp91phox-/-mice, Cell. Microbiol, vol.9, pp.2817-2825, 2007.

D. P. Speert, M. Bond, R. C. Woodman, and J. T. Curnutte, Infection with Pseudomonas cepacia in chronic granulomatous disease: role of nonoxidative killing by neutrophils in host defence, 1994.

, J. Infect. Dis, vol.170, pp.1524-1531

F. Su, M. Juarez, C. L. Cooke, L. Lapointe, J. Shavit et al., , 2007.

T. A. Urban, A. Griffith, A. M. Torok, M. E. Smolkin, J. L. Burns et al., Contribution of Burkholderia cenocepacia flagella to infectivity and inflammation, Infect Immun, vol.72, issue.9, pp.5126-5160, 2004.

M. Van-der-vaart, H. P. Spaink, A. H. Meijer, M. Van-der-vaart, J. J. Van-soest et al., Functional analysis of a zebrafish myd88 mutant identifies key transcriptional components of the innate immune system, Dis. Model. Mech, vol.6, pp.841-854, 2012.

G. M. Ventura, L. Goffic, R. Balloy, V. Plotkowski, M. C. Chignard et al., TLR 5, but neither TLR2 nor TLR4, is involved in lung epithelial cell response to Burkholderia cenocepacia, FEMS Immunol Med Microbiol, vol.54, issue.1, pp.37-44, 2008.

G. M. Ventura, V. Balloy, R. Ramphal, H. Khun, M. Huerre et al., Lack of MyD88 protects the immunodeficient host against fatal lung inflammation triggered by the opportunistic bacteria Burkholderia cenocepacia, J Immunol, vol.183, issue.1, pp.670-676, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00591436

A. C. Vergunst, A. H. Meijer, S. Renshaw, O. 'callaghan, and D. , Burkholderia cenocepacia creates an intramacrophage replication niche in zebrafish embryos, followed by bacterial dissemination and establishment of systemic infection, Infect. Immun, vol.78, pp.1495-1508, 2010.
URL : https://hal.archives-ouvertes.fr/hal-02381194

C. Cui, E. L. Benard, Z. Kanwal, O. W. Stockhammer, M. Van-der-vaart et al., Infectious disease modelling and innate immune function in zebrafish embryos, vol.105, pp.273-308, 2011.

H. Clay, J. M. Davis, D. Beery, A. Huttenlocher, S. E. Lyons et al., , 2007.

, Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish, Cell Host Microbe, vol.2, pp.29-39

P. Darling, M. Chan, A. D. Cox, and P. A. Sokol, Siderophore production by cystic fibrosis isolates of Burkholderia cepacia, Infect. Immun, vol.66, pp.874-877, 1998.

F. Ellett, L. Pase, J. W. Hayman, A. Andrianopoulos, and G. J. Lieschke, Mpeg1 promoter transgenes direct macrophage-lineage expression in zebrafish, Blood, vol.117, pp.49-56, 2011.

S. Glass and J. R. Govan, Pseudomonas cepacia--fatal pulmonary infection in a patient with cystic fibrosis, J. Infect, vol.13, pp.157-158, 1986.

J. Goedhart, D. Von-stetten, M. Noirclerc-savoye, M. Lelimousin, L. Joosen et al., Structure-guided evolution of cyan fluorescent proteins towards a quantum yield of 93%, Nat. Commun, vol.3, p.751, 2012.

J. R. Govan, P. H. Brown, J. Maddison, C. J. Doherty, J. W. Nelson et al., Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis, Lancet, vol.342, pp.15-19, 1993.

C. Gray, C. A. Loynes, M. K. Whyte, D. C. Crossman, S. A. Renshaw et al.,

Y. Feng, C. Santoriello, M. Mione, A. Hurlstone, M. et al., Live imaging of innate immune cell sensing of transformed cells in zebrafish larvae: parallels between tumor initiation and wound inflammation, PLoS Biol, vol.8, p.1000562, 2010.

R. L. Lamason, M. A. Mohideen, J. R. Mest, A. C. Wong, H. L. Norton et al.,

X. Mao, V. R. Humphreville, and J. E. Humbert, SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans, Science, vol.310, issue.5755, pp.1782-1788, 2005.

E. Mahenthiralingam, T. Coenye, J. W. Chung, D. P. Speert, J. R. Govan et al., Diagnostically and experimentally useful panel of strains from the Burkholderia cepacia complex, J. Clin. Microbiol, vol.38, pp.910-913, 2000.

J. Mesureur and A. C. Vergunst, Zebrafish embryos as a model to study bacterial virulence, Methods Mol. Biol, vol.1197, pp.41-66, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02381118

M. Nguyen-chi, Q. T. Phan, C. Gonzalez, J. Dubremetz, J. Levraud et al., Transient infection of the zebrafish notochord with E. coli induces chronic inflammation, Dis. Model. Mech, vol.7, pp.871-882, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02088301

S. A. Renshaw, C. A. Loynes, D. M. Trushell, S. Elworthy, P. W. Ingham et al.,

, A transgenic zebrafish model of neutrophilic inflammation, Blood, vol.108, pp.3976-3978

H. Revets, P. Vandamme, A. Van-zeebroeck, K. De-boeck, M. J. Struelens et al., Burkholderia (Pseudomonas) cepacia and cystic fibrosis: the epidemiology in Belgium, Acta Clin. Belg, vol.51, pp.222-230, 1996.

A. M. Sar, . Van-der, O. W. Stockhammer, C. Laan, . Van-der et al., MyD88 Innate Immune Function in a Zebrafish Embryo Infection Model, vol.74, pp.2436-2441, 2006.

M. Sarris, J. Masson, D. Maurin, L. M. Van-der-aa, P. Boudinot et al., Inflammatory Chemokines Direct and Restrict Leukocyte Migration within Live Tissues as Glycan-Bound Gradients, Curr. Biol, vol.22, pp.2375-2382, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00880492

B. D. Alexander, E. W. Petzold, L. B. Reller, S. M. Palmer, R. D. Davis et al., Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia cepacia complex, Am. J. Transplant, vol.8, pp.1025-1030, 2008.

C. De, G. M. Ventura, R. Le-goffic, V. Balloy, M. Plotkowski et al., TLR 5, but neither TLR2 nor TLR4, is involved in lung epithelial cell response to Burkholderia cenocepacia, FEMS Immunol. Med. Microbiol, vol.54, pp.37-44, 2008.

C. Chaparro, J. Maurer, C. Gutierrez, M. Krajden, C. Chan et al., Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation, Am. J. Respir. Crit. Care Med, vol.163, pp.43-48, 2001.

Y. Y. Chen, C. Chao, F. Liu, P. Hsu, H. Chen et al.,

W. Hsieh and D. S. Wong, Dynamic transcript profiling of Candida albicans infection in zebrafish: a pathogen-host interaction study, PLoS One, vol.8, 2013.

M. V. Cieri, N. Mayer-hamblett, A. Griffith, and J. L. Burns, Correlation between an in vitro invasion assay and a murine model of Burkholderia cepacia lung infection, 2002.

. Immun, , vol.70, pp.1081-1086

C. Cui, E. L. Benard, Z. Kanwal, O. W. Stockhammer, M. Van-der-vaart et al., Infectious disease modeling and innate immune function in zebrafish embryos, 2011.

R. Curciarello, A. Steele, D. Cooper, T. T. Macdonald, L. Kruidenier et al., , 2014.

K. Dedeckova, L. Kalferstova, H. Strnad, J. Vavrova, and P. Drevinek, Novel diagnostic PCR assay for Burkholderia cenocepacia epidemic strain ST32 and its utility in monitoring infection in cystic fibrosis patients, J. Cyst. Fibros, vol.12, pp.475-481, 2013.

M. Dillies, A. Rau, J. Aubert, C. Hennequet-antier, M. Jeanmougin et al., A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00782486

, Bioinform, vol.14, pp.671-683

P. Drevinek and E. Mahenthiralingam, Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence, Clin. Microbiol. Infect, vol.16, pp.821-830, 2010.

P. Drevinek, S. Vosahlikova, O. Cinek, V. Vavrova, J. Bartosova et al., Widespread clone of Burkholderia cenocepacia in cystic fibrosis patients in the Czech Republic, J. Med. Microbiol, vol.54, pp.655-659, 2005.

J. Dumic, S. Dabelic, and M. Flögel, Galectin-3: an open-ended story, 2006.

, Biophys. Acta, vol.1760, pp.616-635

W. R. English, G. Velasco, J. O. Stracke, V. Knäuper, M. et al., Catalytic activities of membrane-type 6 matrix metalloproteinase (MMP25), FEBS Lett, vol.491, pp.137-142, 2001.

Y. Fuchs and H. Steller, Live to die another way: modes of programmed cell death and the signals emanating from dying cells, Nat. Rev. Mol. Cell Biol, vol.16, pp.329-344, 2015.

P. O. Garcin, I. R. Nabi, and N. Panté, Galectin-3 plays a role in minute virus of mice infection, Virology, vol.481, pp.63-72, 2015.

S. Glass and J. R. Govan, Pseudomonas cepacia--fatal pulmonary infection in a patient with cystic fibrosis, J. Infect, vol.13, pp.157-158, 1986.

P. Herbomel, B. Thisse, and C. Thisse, Ontogeny and behaviour of early macrophages in the zebrafish embryo, Development, vol.126, pp.3735-3745, 1999.

R. G. Jenner, Y. , and R. , Insights into host responses against pathogens from transcriptional profiling, Nat. Rev. Microbiol, vol.3, pp.281-294, 2005.

W. M. Johnson, S. D. Tyler, and K. R. Rozee, Linkage analysis of geographic and clinical clusters in Pseudomonas cepacia infections by multilocus enzyme electrophoresis and ribotyping, J. Clin. Microbiol, vol.32, pp.924-930, 1994.

A. M. Jones, M. E. Dodd, J. R. Govan, V. Barcus, C. J. Doherty et al.,

, Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in cystic fibrosis, Thorax, vol.59, pp.948-951

L. Kalferstova, M. Kolar, L. Fila, J. Vavrova, and P. Drevinek, Gene Expression Profiling of Burkholderia cenocepacia at the Time of Cepacia Syndrome: Loss of Motility as a Marker of Poor Prognosis?, J. Clin. Microbiol, vol.53, pp.1515-1522, 2015.

Z. Kanwal, G. F. Wiegertjes, W. J. Veneman, A. H. Meijer, and H. P. Spaink, , 2014.

, Comparative studies of Toll-like receptor signalling using zebrafish, Dev. Comp. Immunol

M. Köthe, M. Antl, B. Huber, K. Stoecker, D. Ebrecht et al., , 2003.

, Killing of Caenorhabditis elegans by Burkholderia cepacia is controlled by the cep quorumsensing system, Cell. Microbiol, vol.5, pp.343-351

G. J. Lieschke, Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish, Blood, vol.98, pp.3087-3096, 2001.

E. Mahenthiralingam, . Baldwin, and C. G. Dowson, Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology, J. Appl. Microbiol, vol.104, pp.1539-1551, 2008.

V. Mariappan, K. M. Vellasamy, J. Thimma, O. H. Hashim, and J. Vadivelu, , 2013.

D. W. Martin and C. D. Mohr, Invasion and Intracellular Survival of Burkholderia cepacia Invasion and Intracellular Survival of Burkholderia cepacia, p.68, 2000.

E. Maza, P. Frasse, P. Senin, M. Bouzayen, and M. Zouine, Comparison of normalization methods for differential gene expression analysis in RNA-Seq experiments, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00982548

, Commun. Integr. Biol, vol.6, p.25849

A. H. Meijer, S. Gabby-krens, I. A. Medina-rodriguez, S. He, W. Bitter et al., Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish, Mol. Immunol, vol.40, pp.773-783, 2004.

J. Mesureur and A. C. Vergunst, Zebrafish embryos as a model to study bacterial virulence, Methods Mol. Biol, vol.1197, pp.41-66, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02381118

B. Novoa, T. V. Bowman, L. Zon, and A. Figueras, LPS response and tolerance in the zebrafish (Danio rerio), Fish Shellfish Immunol, vol.26, pp.326-331, 2009.

E. P. O'grady and P. A. Sokol, Burkholderia cenocepacia differential gene expression during host-pathogen interactions and adaptation to the host environment, Front. Cell. Infect. Microbiol, vol.1, p.15, 2011.

A. Ordas, Z. Kanwal, V. Lindenberg, J. Rougeot, M. Mink et al.,

M. De-perrot, C. Chaparro, K. Mcrae, T. K. Waddell, D. Hadjiliadis et al., Twenty-year experience of lung transplantation at a single center: Influence of recipient diagnosis on long-term survival, J. Thorac. Cardiovasc, 2004.

. Surg, , vol.127, pp.1493-1501

N. L. Podnecky, K. A. Rhodes, and H. P. Schweizer, , 2015.

L. Ramakrishnan, The zebrafish guide to tuberculosis immunity and treatment, Cold Spring Harb. Symp. Quant. Biol, vol.78, pp.179-192, 2013.

K. Reddi, S. B. Phagoo, K. D. Anderson, and D. Warburton, Burkholderia cepaciainduced IL-8 gene expression in an alveolar epithelial cell line: signaling through CD14 and mitogen-activated protein kinase, Pediatr. Res, vol.54, pp.297-305, 2003.

R. Reik, T. Spilker, and J. J. Lipuma, Distribution of Burkholderia cepacia complex species among isolates recovered from persons with or without cystic fibrosis, J. Clin, 2005.

. Microbiol, , vol.43, pp.2926-2928

S. Renshaw, C. Loynes, D. M. Trushell, S. Elworthy, P. W. Ingham et al.,

, A transgenic zebrafish model of neutrophilic inflammation, Blood, vol.108, pp.3976-3978

S. Sato, P. Bhaumik, G. St-pierre, and I. Pelletier, Role of galectin-3 in the initial control of Leishmania infection, Crit. Rev. Immunol, vol.34, pp.147-175, 2014.

E. Schutyser, S. Struyf, and J. Van-damme, The CC chemokine CCL20 and its receptor CCR6, Cytokine Growth Factor Rev, vol.14, pp.409-426, 2003.

K. D. Seed and J. J. Dennis, Development of Galleria mellonella as an alternative infection model for the Burkholderia cepacia complex, Infect. Immun, vol.76, pp.1267-1275, 2008.

M. P. Sepulcre, F. Alcaraz-pérez, A. López-muñoz, F. J. Roca, J. Meseguer et al., Evolution of lipopolysaccharide (LPS) recognition and signaling: fish TLR4 does not recognize LPS and negatively regulates NF-kappaB activation, J. Immunol, vol.182, pp.1836-1845, 2009.

P. A. Sokol, P. Darling, D. E. Woods, E. Mahenthiralingam, and C. Kooi, Role of ornibactin biosynthesis in the virulence of Burkholderia cepacia: characterization of pvdA, the gene encoding L-ornithine N(5)-oxygenase, Infect. Immun, vol.67, pp.4443-4455, 1999.

A. De-soyza, G. Meachery, K. L. Hester, A. Nicholson, G. Parry et al.,

S. Clark, J. L. Lordan, and S. Schueler, Lung transplantation for patients with cystic 220, 2010.

S. Zhang and P. Cui, Complement system in zebrafish, Dev. Comp. Immunol, 2014.

J. E. Zlosnik, L. C. Gunaratnam, and D. P. Speert, Serum susceptibility in clinical isolates of Burkholderia cepacia complex bacteria: development of a growth-based assay for high throughput determination, Front. Cell. Infect. Microbiol, vol.2, p.67, 2012.

B. A. Abdulrahman, A. A. Khweek, A. Akhter, K. Caution, S. Kotrange et al., Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis, Autophagy, vol.7, pp.1359-1370, 2011.

B. A. Abdulrahman, A. A. Khweek, A. Akhter, K. Caution, M. Tazi et al., Depletion of the ubiquitin-binding adaptor molecule SQSTM1/p62 from macrophages harboring cftr ?F508 mutation improves the delivery of Burkholderia cenocepacia to the autophagic machinery, J. Biol. Chem, vol.288, pp.2049-2058, 2013.

K. Agnoli, S. Schwager, S. Uehlinger, A. Vergunst, D. F. Viteri et al., Exposing the third chromosome of Burkholderia cepacia complex strains as a virulence plasmid, Mol. Microbiol, vol.83, pp.362-378, 2012.
URL : https://hal.archives-ouvertes.fr/hal-02381171

K. Agnoli, C. Frauenknecht, R. Freitag, S. Schwager, C. Jenul et al., The third replicon of members of the Burkholderia cepacia complex, plasmid pC3, plays a role in stress tolerance, Appl. Environ. Microbiol, vol.80, issue.4, pp.1340-1348, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02381128

B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts et al., Cell Biology of Infection, 2002.

S. Al-khodor, K. Marshall-batty, V. Nair, L. Ding, D. E. Greenberg et al., , 2014.

, Burkholderia cenocepacia J2315 escapes to the cytosol and actively subverts autophagy in human macrophages, Cell. Microbiol, vol.16, pp.378-395

L. H. Allen, Mechanisms of pathogenesis: evasion of killing by polymorphonuclear leukocytes, Microbes Infect, vol.5, pp.1329-1335, 2003.

A. Angot, A. Vergunst, S. Genin, and N. Peeters, Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems, PLoS Pathog, vol.3, p.3, 2007.

D. F. Aubert, R. S. Flannagan, and M. A. Valvano, A novel sensor kinase-response regulator hybrid controls biofilm formation and type VI secretion system activity in Burkholderia cenocepacia, Infect. Immun, vol.76, pp.1979-1991, 2008.

A. Baldwin, E. Mahenthiralingam, K. M. Thickett, D. Honeybourne, M. C. Maiden et al., Multilocus sequence typing scheme that provides both species and strain differentiation for the Burkholderia cepacia complex, J. Clin. Microbiol, vol.43, pp.4665-4673, 2005.

S. Bamford, H. Ryley, J. , and S. K. , Highly purified lipopolysaccharides from Burkholderia cepacia complex clinical isolates induce inflammatory cytokine responses via TLR4-mediated MAPK signalling pathways and activation of NFkappaB, Cell. Microbiol, vol.9, pp.532-543, 2007.

K. Beiter, F. Wartha, B. Albiger, S. Normark, A. Zychlinsky et al., An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps, Curr. Biol, vol.16, pp.401-407, 2006.

E. T. Berends, A. R. Horswill, N. M. Haste, M. Monestier, V. Nizet et al., Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps, J. Innate Immun, vol.2, pp.576-586, 2010.

S. P. Bernier, L. Silo-suh, D. E. Woods, D. E. Ohman, and P. A. Sokol, Comparative analysis of plant and animal models for characterization of Burkholderia cepacia virulence, Infect. Immun, vol.71, pp.5306-5313, 2003.

J. Y. Bertrand, A. D. Kim, E. P. Violette, D. L. Stachura, J. L. Cisson et al., Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo, Development, vol.134, pp.4147-4156, 2007.

C. J. Blohmke, R. E. Victor, A. F. Hirschfeld, I. M. Elias, D. G. Hancock et al., Innate immunity mediated by TLR5 as a novel antiinflammatory target for cystic fibrosis lung disease, J. Immunol, vol.180, pp.7764-7773, 2008.

H. Boshra, J. Li, and J. O. Sunyer, Recent advances on the complement system of teleost fish, Fish Shellfish Immunol, vol.20, pp.239-262, 2006.

J. Van-den-bossche, A. E. Neele, M. A. Hoeksema, and M. P. De-winther, Macrophage polarization: the epigenetic point of view, Curr. Opin. Lipidol, vol.25, pp.367-373, 2014.

T. V. Bowman and L. I. Zon, Swimming into the future of drug discovery: in vivo chemical screens in zebrafish, ACS Chem. Biol, vol.5, pp.159-161, 2010.

A. Bragonzi, Murine models of acute and chronic lung infection with cystic fibrosis pathogens, Int. J. Med. Microbiol, vol.300, pp.584-593, 2010.

V. Brinkmann and A. Zychlinsky, Neutrophil extracellular traps: is immunity the second function of chromatin?, J. Cell Biol, vol.198, pp.773-783, 2012.

V. Brinkmann, U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann et al., Neutrophil extracellular traps kill bacteria, Science, vol.303, pp.1532-1535, 2004.

S. Brockbank, D. Downey, J. S. Elborn, and M. Ennis, Effect of cystic fibrosis exacerbations on neutrophil function, Int. Immunopharmacol, vol.5, pp.601-608, 2005.

K. M. Brothers, Z. R. Newman, and R. T. Wheeler, Live imaging of disseminated candidiasis in zebrafish reveals role of phagocyte oxidase in limiting filamentous growth, Eukaryot. Cell, vol.10, pp.932-944, 2011.

P. Broz, K. Newton, M. Lamkanfi, S. Mariathasan, V. M. Dixit et al., Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella, J. Exp. Med, vol.207, pp.1745-1755, 2010.

J. T. Buchanan, A. J. Simpson, R. K. Aziz, G. Y. Liu, S. A. Kristian et al., DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps, Curr. Biol, vol.16, pp.396-400, 2006.

J. S. Burgos, J. Ripoll-gomez, J. M. Alfaro, I. Sastre, and F. Valdivieso, Zebrafish as a new model for herpes simplex virus type 1 infection, Zebrafish, vol.5, pp.323-333, 2008.

W. H. Burkholder, Bacteria as plant pathogens, Annu. Rev. Microbiol, vol.2, issue.1, pp.389-412, 1948.

J. L. Burns, M. Jonas, E. Y. Chi, D. K. Clark, A. Berger et al., Invasion of respiratory epithelial cells by Burkholderia (Pseudomonas) cepacia, Infect. Immun, vol.64, pp.4054-4059, 1996.

J. Bylund, P. A. Campsall, R. C. Ma, B. D. Conway, and D. P. Speert, Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease, J. Immunol, vol.174, pp.3562-3569, 2005.

J. Bylund, L. Burgess, P. Cescutti, R. K. Ernst, and D. P. Speert, Exopolysaccharides from Burkholderia cenocepacia inhibit neutrophil chemotaxis and scavenge reactive oxygen species, J. Biol. Chem, vol.281, pp.2526-2532, 2006.

C. De, G. M. Ventura, R. Le-goffic, V. Balloy, M. Plotkowski et al., , 2008.

, TLR 5, but neither TLR2 nor TLR4, is involved in lung epithelial cell response to Burkholderia cenocepacia, FEMS Immunol. Med. Microbiol, vol.54, pp.37-44

R. Carvalho, J. De-sonneville, O. W. Stockhammer, N. D. Savage, W. J. Veneman et al., A high-throughput screen for tuberculosis progression, PLoS One, vol.6, 2011.

J. Castonguay-vanier, L. Vial, J. Tremblay, and E. Déziel, Drosophila melanogaster as a model host for the Burkholderia cepacia complex, PLoS One, vol.5, 2010.
URL : https://hal.archives-ouvertes.fr/pasteur-00547901

J. Celli, The changing nature of the Brucella-containing vacuole, Cell. Microbiol, vol.17, issue.7, p.261, 2015.

A. Chavan and S. Mukherji, Treatment of hydrocarbon-rich wastewater using oil degrading bacteria and phototrophic microorganisms in rotating biological contactor: effect of N:P ratio, J. Hazard. Mater, vol.154, pp.63-72, 2008.

Y. Y. Chen, C. Chao, F. Liu, P. Hsu, H. Chen et al., Dynamic transcript profiling of Candida albicans infection in zebrafish: a pathogen-host interaction study, PLoS One, vol.8, 2013.

J. W. Chung and D. P. Speert, Proteomic identification and characterization of bacterial factors associated with Burkholderia cenocepacia survival in a murine host, Microbiology, vol.153, pp.206-214, 2007.

M. V. Cieri, N. Mayer-hamblett, A. Griffith, and J. L. Burns, Correlation between an in vitro invasion assay and a murine model of Burkholderia cepacia lung infection, Infect. Immun, vol.70, pp.1081-1086, 2002.

H. Clay, J. M. Davis, D. Beery, A. Huttenlocher, S. E. Lyons et al., , 2007.

, Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish, Cell Host Microbe, vol.2, pp.29-39

T. Coenye, P. Vandamme, J. R. Govan, and J. J. Lipuma, Taxonomy and Identification of the Burkholderia cepacia Complex, J. Clin. Microbiol, vol.39, pp.3427-3436, 2001.

E. Colucci-guyon, J. Tinevez, S. Renshaw, and P. Herbomel, Strategies of professional phagocytes in vivo: unlike macrophages, neutrophils engulf only surface-associated microbes, J. Cell Sci, pp.3053-3059, 2011.
URL : https://hal.archives-ouvertes.fr/pasteur-02616471

B. D. Conway, K. K. Chu, J. Bylund, E. Altman, and D. P. Speert, Production of exopolysaccharide by Burkholderia cenocepacia results in altered cell-surface interactions and altered bacterial clearance in mice, J. Infect. Dis, vol.190, pp.957-966, 2004.

M. R. Cronan and D. M. Tobin, Fit for consumption: zebrafish as a model for tuberculosis, Dis. Model. Mech, vol.7, pp.777-784, 2014.

C. Cui, E. L. Benard, Z. Kanwal, O. W. Stockhammer, M. Van-der-vaart et al., Infectious disease modeling and innate immune function in zebrafish embryos, 2011.

H. D'hauteville, S. Khan, D. J. Maskell, A. Kussak, A. Weintraub et al., Two msbB genes encoding maximal acylation of lipid A are required for invasive Shigella flexneri to mediate inflammatory rupture and destruction of the intestinal epithelium, J. Immunol, vol.168, pp.5240-5251, 2002.

R. P. Darveau, S. Arbabi, I. Garcia, B. Bainbridge, and R. Maier, Porphyromonas gingivalis lipopolysaccharide is both agonist and antagonist for p38 mitogen-activated protein kinase activation, Infect. Immun, vol.70, pp.1867-1873, 2002.

J. M. Davis, H. Clay, J. L. Lewis, N. Ghori, P. Herbomel et al., Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos, Immunity, vol.17, pp.693-702, 2002.

Y. Deng, C. Boon, L. Eberl, and L. Zhang, Differential modulation of Burkholderia cenocepacia virulence and energy metabolism by the quorum-sensing signal BDSF and its synthase, J. Bacteriol, vol.191, pp.7270-7278, 2009.

S. Dewitt, I. Laffafian, and M. B. Hallett, Phagosomal oxidative activity during beta2 integrin (CR3)-mediated phagocytosis by neutrophils is triggered by a non-restricted Ca2+ signal: Ca2+ controls time not space, J. Cell Sci, vol.116, pp.2857-2865, 2003.

C. Ding, J. Zhang, Y. Zhao, Z. Peng, D. Song et al., Zebrafish as a potential model organism for drug test against hepatitis C virus, PLoS One, vol.6, 2011.

C. Ding, Y. Zhao, J. Zhang, Z. Peng, D. Song et al., A zebrafish model for subgenomic hepatitis C virus replication, Int. J. Mol. Med, vol.35, pp.791-797, 2015.

G. Dranoff, Cytokines in cancer pathogenesis and cancer therapy, Nat. Rev. Cancer, vol.4, pp.11-22, 2004.

P. Drevinek and E. Mahenthiralingam, Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence, Clin. Microbiol. Infect, vol.16, pp.821-830, 2010.

P. Encinas, M. A. Rodriguez-milla, B. Novoa, A. Estepa, A. Figueras et al., Zebrafish fin immune responses during high mortality infections with viral haemorrhagic septicemia rhabdovirus. A proteomic and transcriptomic approach, BMC Genomics, vol.11, p.518, 2010.

M. Fazli, H. Almblad, M. L. Rybtke, M. Givskov, L. Eberl et al., Regulation of biofilm formation in Pseudomonas and Burkholderia species, Environ. Microbiol, vol.16, pp.1961-1981, 2014.

J. Fink, J. H. Steer, D. A. Joyce, A. S. Mcwilliam, and G. A. Stewart, Pro-inflammatory effects of Burkholderia cepacia on cystic fibrosis respiratory epithelium, FEMS Immunol. Med. Microbiol, vol.38, pp.273-282, 2003.

R. S. Flannagan, V. Jaumouillé, K. K. Huynh, J. D. Plumb, G. P. Downey et al., Burkholderia cenocepacia disrupts host cell actin cytoskeleton by inactivating Rac and Cdc42, Cell. Microbiol, vol.14, pp.239-254, 2012.

L. Franchi, T. Eigenbrod, R. Muñoz-planillo, and G. Nuñez, The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis, Nat. Immunol, vol.10, pp.241-247, 2009.

T. A. Fuchs, U. Abed, C. Goosmann, R. Hurwitz, I. Schulze et al., Novel cell death program leads to neutrophil extracellular traps, J. Cell Biol, vol.176, pp.231-241, 2007.

K. A. Gabor, M. F. Goody, W. K. Mowel, M. E. Breitbach, R. L. Gratacap et al., Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment, Dis. Model. Mech, vol.7, pp.1227-1237, 2014.

S. Ganesan and U. S. Sajjan, Host Evasion by Burkholderia cenocepacia, Front. Cell. Infect. Microbiol, vol.1, p.25, 2011.

A. H. Gaspar and M. P. Machner, VipD is a Rab5-activated phospholipase A1 that protects Legionella pneumophila from endosomal fusion, Proc. Natl. Acad. Sci. U. S. A, vol.111, pp.4560-4565, 2014.

M. Gavrilin, D. H. Abdelaziz, M. Mostafa, B. Abdulrahman, J. Grandhi et al., Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia, J. Immunol, vol.188, pp.3469-3477, 2012.

C. Genestet, A. Le-gouellec, H. Chaker, B. Polack, B. Guery et al., Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing. Free Radic, Biol. Med, vol.73, pp.400-410, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01464090

D. D. Gillette, P. Shah, T. Cremer, M. Gavrilin, B. Y. Besecker et al., Analysis of human bronchial epithelial eell proinflammatory response to Burkholderia cenocepacia Infection: inability to secrete IL-1?, J. Biol. Chem, vol.288, pp.3691-3695, 2013.

L. Gong, M. Cullinane, P. Treerat, G. Ramm, M. Prescott et al., The Burkholderia pseudomallei type III secretion system and BopA are required for evasion of LC3-associated phagocytosis, PLoS One, vol.6, p.17852, 2011.

M. F. Goody, C. Sullivan, and C. H. Kim, Studying the immune response to human viral infections using zebrafish, Dev. Comp. Immunol, vol.46, pp.84-95, 2014.

M. Govindarajan, J. Balandreau, R. Muthukumarasamy, G. Revathi, and C. Lakshminarasimhan,

R. L. Gratacap and R. T. Wheeler, Utilization of zebrafish for intravital study of eukaryotic pathogen-host interactions, Dev. Comp. Immunol, vol.46, pp.108-115, 2014.

O. Gross, Measuring the inflammasome, Methods Mol. Biol, vol.844, pp.199-222, 2012.

L. Guyader, D. Redd, M. J. Colucci-guyon, E. Murayama, E. Kissa et al., Origins and unconventional behavior of neutrophils in developing zebrafish, Blood, vol.111, pp.132-141, 2008.
URL : https://hal.archives-ouvertes.fr/pasteur-02558365

A. Hakkim, T. A. Fuchs, N. E. Martinez, S. Hess, H. Prinz et al., Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation, Nat. Chem. Biol, vol.7, pp.75-77, 2011.

T. W. Halverson, M. Wilton, K. K. Poon, B. Petri, and S. Lewenza, DNA is an antimicrobial component of eutrophil Extracellular Traps, PLOS Pathog, vol.11, p.1004593, 2015.

A. Hanuszkiewicz, P. Pittock, F. Humphries, H. Moll, A. R. Rosales et al., Identification of the flagellin glycosylation system in Burkholderia cenocepacia and the contribution of glycosylated flagellin to evasion of human innate immune responses, J. Biol. Chem, vol.289, pp.19231-19244, 2014.

Z. Hegedus, A. Zakrzewska, V. C. Agoston, A. Ordas, P. Rácz et al., Deep sequencing of the zebrafish transcriptome response to mycobacterium infection, Mol. Immunol, vol.46, pp.2918-2930, 2009.

P. Herbomel, B. Thisse, and C. Thisse, Ontogeny and behaviour of early macrophages in the zebrafish embryo, Development, vol.126, pp.3735-3745, 1999.

M. J. Hickey and P. Kubes, Intravascular immunity: the host-pathogen encounter in blood vessels, Nat. Rev. Immunol, vol.9, pp.364-375, 2009.

R. Hosseini, G. E. Lamers, Z. Hodzic, A. H. Meijer, M. J. Schaaf et al., Correlative light and electron microscopy imaging of autophagy in a zebrafish infection model, Autophagy, vol.10, pp.1844-1857, 2014.

M. L. Hutchison, I. R. Poxton, and J. R. Govan, Burkholderia cepacia produces a hemolysin that is capable of inducing apoptosis and degranulation of mammalian phagocytes, Infect. Immun, vol.66, pp.2033-2039, 1998.

K. K. Huynh, J. D. Plumb, G. P. Downey, M. Valvano, G. et al., Inactivation of macrophage Rab7 by Burkholderia cenocepacia, J. Innate Immun, vol.2, pp.522-533, 2010.

J. L. Jacobs, A. C. Fasi, A. Ramette, J. J. Smith, R. Hammerschmidt et al., Identification and onion pathogenicity of Burkholderia cepacia complex isolates from the onion rhizosphere and onion field soil, Appl. Environ. Microbiol, vol.74, pp.3121-3129, 2008.

M. E. Jaconi, D. P. Lew, J. L. Carpentier, K. E. Magnusson, M. Sjögren et al., , 1990.

, Cytosolic free calcium elevation mediates the phagosome-lysosome fusion during phagocytosis in human neutrophils, J. Cell Biol, vol.110, pp.1555-1564

M. Jagannathan-bogdan and L. I. Zon, Hematopoiesis. Development, vol.140, pp.2463-2467, 2013.

C. Jault, L. Pichon, and J. Chluba, Toll-like receptor gene family and TIR-domain adapters in Danio rerio, Mol. Immunol, vol.40, pp.759-771, 2004.

V. Jaumouillé and S. Grinstein, Receptor mobility, the cytoskeleton, and particle binding during phagocytosis, Curr. Opin. Cell Biol, vol.23, pp.22-29, 2011.

H. Jin, R. Sood, J. Xu, F. Zhen, M. A. English et al., Definitive hematopoietic stem/progenitor cells manifest distinct differentiation output in the zebrafish VDA and PBI, Development, vol.136, pp.647-654, 2009.

B. Jundi, K. Pohl, and E. Reeves, The importance of CFTR expression for neutrophil function in patients with Cystic Fibrosis, BMC Proc, vol.9, p.36, 2015.

Z. Kanwal, G. F. Wiegertjes, W. J. Veneman, A. H. Meijer, and H. P. Spaink, Comparative studies of Toll-like receptor signalling using zebrafish, Dev. Comp. Immunol, 2014.

T. Kawai, A. , and S. , The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors, Nat. Immunol, vol.11, pp.373-384, 2010.

K. Kawasaki, R. K. Ernst, and S. I. Miller, 3-O-deacylation of lipid A by PagL, a PhoP/PhoQregulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4, J. Biol. Chem, vol.279, 2004.

S. K. Kaza, S. Mcclean, and M. Callaghan, IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteria, Int. J. Med. Microbiol, vol.301, pp.26-33, 2011.

K. E. Keith, D. W. Hynes, J. E. Sholdice, and M. A. Valvano, Delayed association of the NADPH oxidase complex with macrophage vacuoles containing the opportunistic pathogen Burkholderia cenocepacia, Microbiology, vol.155, pp.1004-1015, 2009.

M. C. Kerr and R. D. Teasdale, Defining macropinocytosis, Traffic, vol.10, pp.364-371, 2009.

B. P. Knox, Q. Deng, M. Rood, J. C. Eickhoff, N. P. Keller et al., Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and hyphae in zebrafish larvae, Eukaryot. Cell, vol.13, pp.1266-1277, 2014.

C. Kooi, Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides, Microbiology, vol.155, pp.2818-2825, 2009.

M. Köthe, M. Antl, B. Huber, K. Stoecker, D. Ebrecht et al., Killing of Caenorhabditis elegans by Burkholderia cepacia is controlled by the cep quorum-sensing system, Cell. Microbiol, vol.5, pp.343-351, 2003.

S. Lai and R. J. Devenish, LC3-Associated Phagocytosis (LAP), vol.1, pp.396-408, 2012.

S. H. Lam, H. L. Chua, Z. Gong, T. J. Lam, and Y. M. Sin, Development and maturation of the immune system in zebrafish, Danio rerio: a gene expression profiling, in situ hybridization and immunological study, Dev. & Comp Immun, vol.28, pp.9-28, 2004.

J. Lamothe and M. A. Valvano, Burkholderia cenocepacia-induced delay of acidification and phagolysosomal fusion in cystic fibrosis transmembrane conductance regulator (CFTR)-defective macrophages, Microbiology, vol.154, pp.3825-3834, 2008.

J. Lamothe, S. Thyssen, and M. A. Valvano, Burkholderia cepacia complex isolates survive intracellularly without replication within acidic vacuoles of Acanthamoeba polyphaga, Cell. Microbiol, vol.6, pp.1127-1138, 2004.

J. Lamothe, K. K. Huynh, S. Grinstein, and M. Valvano, Intracellular survival of Burkholderia cenocepacia in macrophages is associated with a delay in the maturation of bacteria-containing vacuoles, Cell. Microbiol, vol.9, pp.40-53, 2007.

E. Latz, T. S. Xiao, and A. Stutz, Activation and regulation of the inflammasomes, Nat. Rev. Immunol, vol.13, pp.397-411, 2013.

E. J. Lee, M. H. Pontes, and E. A. Groisman, A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1F0 ATP synthase, Cell, vol.154, pp.146-156, 2013.

B. Lemaitre, E. Nicolas, L. Michaut, J. M. Reichhart, and J. A. Hoffmann, The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults, Cell, vol.86, pp.973-983, 1996.

J. Levraud, O. Disson, K. Kissa, I. Bonne, P. Cossart et al., Realtime observation of Listeria monocytogenes-phagocyte interactions in living zebrafish larvae, Infect. Immun, vol.77, pp.3651-3660, 2009.

G. J. Lieschke, Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish, Blood, vol.98, pp.3087-3096, 2001.

B. Lin, S. Chen, Z. Cao, Y. Lin, D. Mo et al., Acute phase response in zebrafish upon Aeromonas salmonicida and Staphylococcus aureus infection: striking similarities and obvious differences with mammals, Mol. Immunol, vol.44, pp.295-301, 2007.

S. Loutet and M. Valvano, A decade of Burkholderia cenocepacia virulence determinant research, Infect. Immun, vol.78, pp.4088-4100, 2010.

B. Lubamba, B. Dhooghe, S. Noel, and T. Leal, Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy, Clin. Biochem, vol.45, pp.1132-1144, 2012.

K. L. Macdonald and D. P. Speert, Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cells, Cell. Microbiol, vol.10, pp.2138-2149, 2008.

N. E. Madala, A. Molinaro, and I. A. Dubery, Distinct carbohydrate and lipid-based molecular patterns within lipopolysaccharides from Burkholderia cepacia contribute to defense-associated differential gene expression in Arabidopsis thaliana, Innate Immun, vol.18, pp.140-154, 2012.

E. Mahenthiralingam, J. Bischof, S. K. Byrne, C. Radomski, J. E. Davies et al., DNA-Based diagnostic approaches for identification of Burkholderia cepacia complex, Burkholderia vietnamiensis, Burkholderia multivorans, Burkholderia stabilis, and Burkholderia cepacia genomovars I and III, J. Clin. Microbiol, vol.38, pp.3165-3173, 2000.

K. E. Maloney and M. A. Valvano, The mgtC gene of Burkholderia cenocepacia is required for growth under magnesium limitation conditions and intracellular survival in macrophages, Infect. Immun, vol.74, pp.5477-5486, 2006.

V. Marcos, Z. Zhou-suckow, A. Önder-yildirim, A. Bohla, A. Hector et al., Free DNA in cystic fibrosis airway fluids correlates with airflow obstruction, Mediators Inflamm, p.408935, 2015.

V. Mariappan, K. M. Vellasamy, J. Thimma, O. H. Hashim, and J. Vadivelu, Infection of Burkholderia cepacia induces homeostatic responses in the host for their prolonged survival: the microarray perspective, PLoS One, vol.8, p.77418, 2013.

D. W. Martin and C. D. Mohr, Invasion and intracellular survival of Burkholderia cepacia invasion and intracellular survival of Burkholderia cepacia, Infect. Immun, vol.68, issue.1, p.24, 2000.

A. Matsuo, H. Oshiumi, T. Tsujita, H. Mitani, H. Kasai et al., Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses, J. Immunol, vol.181, pp.3474-3485, 2008.

G. Mayer, Immunology -Chapter One Innate (Non-specific) Immunity, 2010.

S. Mckeon, S. Mcclean, and M. Callaghan, Macrophage responses to CF pathogens: JNK MAP kinase signaling by Burkholderia cepacia complex lipopolysaccharide, FEMS Immunol. Med. Microbiol, vol.60, pp.36-43, 2010.

R. Medzhitov, P. Preston-hurlburt, and C. A. Janeway, A human homologue of the Drosophila Toll protein signals activation of adaptive immunity, Nature, vol.388, pp.394-397, 1997.

N. D. Meeker and N. S. Trede, Immunology and zebrafish: spawning new models of human disease, Dev. Comp. Immunol, vol.32, pp.745-757, 2008.

A. H. Meijer, S. Gabby-krens, I. A. Medina-rodriguez, S. He, W. Bitter et al., Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish, Mol. Immunol, vol.40, pp.773-783, 2004.

A. H. Meijer, M. Van-der-vaart, and H. P. Spaink, Real-time imaging and genetic dissection of host-microbe interactions in zebrafish, Cell. Microbiol, 2013.

J. Mesureur and A. C. Vergunst, Zebrafish embryos as a model to study bacterial virulence, Methods Mol. Biol, vol.1197, pp.41-66, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02381118

K. D. Metzler, T. A. Fuchs, W. M. Nauseef, D. Reumaux, J. Roesler et al., Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity, Blood, vol.117, pp.953-959, 2011.

S. Mostowy, L. Boucontet, M. J. Mazon-moya, A. Sirianni, P. Boudinot et al., The Zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy, PLoS Pathog, vol.9, 2013.
URL : https://hal.archives-ouvertes.fr/hal-02650798

J. A. Moura, M. Cristina-de-assis, G. C. Ventura, A. M. Saliba, L. Gonzaga et al., Differential interaction of bacterial species from the Burkholderia cepacia complex with human airway epithelial cells, Microbes Infect, vol.10, pp.52-59, 2008.

W. M. Nauseef and N. Borregaard, Neutrophils at work, Nat. Immunol, vol.15, pp.602-611, 2014.

B. Novoa, T. V. Bowman, L. Zon, and A. Figueras, LPS response and tolerance in the zebrafish (Danio rerio), Fish Shellfish Immunol, vol.26, pp.326-331, 2009.

E. P. O'grady, D. T. Nguyen, L. Weisskopf, L. Eberl, and P. Sokol, The Burkholderia cenocepacia LysR-type transcriptional regulator ShvR influences expression of quorum-sensing, protease, type II secretion, and afc genes, J. Bacteriol, vol.193, pp.163-176, 2011.

M. Ogawa, T. Yoshimori, T. Suzuki, H. Sagara, N. Mizushima et al., Escape of intracellular Shigella from autophagy, Science, vol.307, pp.727-731, 2005.

A. Ortega-gómez, M. Perretti, and O. Soehnlein, Resolution of inflammation: an integrated view, EMBO Mol. Med, vol.5, pp.661-674, 2013.

R. G. Painter, V. G. Valentine, N. A. Lanson, K. Leidal, Q. Zhang et al., CFTR Expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis, Biochemistry, vol.45, pp.10260-10269, 2006.

N. Palha, F. Guivel-benhassine, V. Briolat, G. Lutfalla, M. Sourisseau et al., Real-time whole-body visualization of Chikungunya Virus infection and host interferon response in zebrafish, PLoS Pathog, vol.9, p.1003619, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01109454

D. Pali?, C. B. Andreasen, J. Ostoji?, R. M. Tell, and J. Roth, Zebrafish (Danio rerio) whole kidney assays to measure neutrophil extracellular trap release and degranulation of primary granules, J. Immunol. Methods, vol.319, pp.87-97, 2007.

Z. Pancer and M. D. Cooper, The evolution of adaptive immunity, Annu. Rev. Immunol, vol.24, pp.497-518, 2006.

M. C. Papaleo, E. Perrin, I. Maida, M. Fondi, R. Fani et al., Identification of species of the Burkholderia cepacia complex by sequence analysis of the hisA gene, J. Med. Microbiol, vol.59, pp.1163-1170, 2010.

V. Papayannopoulos, K. D. Metzler, A. Hakkim, and A. Zychlinsky, Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps, J. Cell Biol, vol.191, pp.677-691, 2010.

S. S. Pedersen, A. Kharazmi, F. Espersen, and N. Høiby, Pseudomonas aeruginosa alginate in cystic fibrosis sputum and the inflammatory response, Infect. Immun, vol.58, pp.3363-3368, 1990.

D. Pietretti, M. Scheer, I. R. Fink, N. Taverne, H. F. Savelkoul et al., Identification and functional characterization of nonmammalian Toll-like receptor 20, Immunogenetics, vol.66, pp.123-141, 2014.

L. Pirone, A. Bragonzi, A. Farcomeni, M. Paroni, C. Auriche et al., Burkholderia cenocepacia strains isolated from cystic fibrosis patients are apparently more invasive and more virulent than rhizosphere strains, Environ. Microbiol, vol.10, pp.2773-2784, 2008.

A. Pizzolla, M. Hultqvist, B. Nilson, M. J. Grimm, T. Eneljung et al., Reactive oxygen species produced by the NADPH oxidase 2 complex in monocytes protect mice from bacterial infections, J. Immunol, vol.188, pp.5003-5011, 2012.

K. Pohl, E. Hayes, J. Keenan, M. Henry, P. Meleady et al., A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy, Blood, vol.124, pp.999-1009, 2014.

L. Porter and J. B. Goldberg, Influence of neutrophil defects on Burkholderia cepacia complex pathogenesis, Front. Cell. Infect. Microbiol, vol.1, p.9, 2011.

D. A. Portnoy, Manipulation of innate immunity by bacterial pathogens, Curr. Opin. Immunol, vol.17, pp.25-28, 2005.

T. K. Prajsnar, V. T. Cunliffe, S. J. Foster, and S. A. Renshaw, A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens, Cell. Microbiol, vol.10, pp.2312-2325, 2008.

L. Ramakrishnan, The zebrafish guide to tuberculosis immunity and treatment, Cold Spring Harb. Symp. Quant. Biol, vol.78, pp.179-192, 2013.

A. Ramette, J. J. Lipuma, and J. M. Tiedje, Species abundance and diversity of Burkholderia cepacia complex in the environment, Appl. Environ. Microbiol, vol.71, pp.1193-1201, 2005.

R. Rebeil, R. K. Ernst, B. B. Gowen, S. I. Miller, and B. J. Hinnebusch, Variation in lipid A structure in the pathogenic Yersiniae, Mol. Microbiol, vol.52, pp.1363-1373, 2004.

K. Reddi, S. B. Phagoo, K. D. Anderson, and D. Warburton, Burkholderia cepacia-induced IL-8 gene expression in an alveolar epithelial cell line: signaling through CD14 and mitogen-activated protein kinase, Pediatr. Res, vol.54, pp.297-305, 2003.

S. A. Renshaw and N. S. Trede, A model 450 million years in the making : zebrafish and vertebrate immunity, Perspective, vol.47, pp.38-47, 2012.

R. Rosales-reyes, A. M. Skeldon, D. F. Aubert, and M. Valvano, The Type VI secretion system of Burkholderia cenocepacia affects multiple Rho family GTPases disrupting the actin cytoskeleton and the assembly of NADPH oxidase complex in macrophages, Cell. Microbiol, vol.14, pp.255-273, 2012.

R. Rosales-reyes, D. F. Aubert, J. S. Tolman, A. O. Amer, and V. , Burkholderia cenocepacia type VI secretion system mediates escape of type II secreted proteins into the cytoplasm of infected macrophages, PLoS One, vol.7, 2012.

H. Rus, C. Cudrici, and F. Niculescu, The role of the complement system in innate immunity, Immunol. Res, vol.33, pp.103-112, 2005.

L. S. Saini, S. B. Galsworthy, and . John, , 1999.

S. U. Sajjan, L. A. Carmody, C. F. Gonzalez, and J. J. Lipuma, A type IV secretion system contributes to intracellular survival and replication of Burkholderia cenocepacia, Infect. Immun, vol.76, pp.5447-5455, 2008.

U. Sajjan, C. Ackerley, and J. Forstner, Interaction of cblA/adhesin-positive Burkholderia cepacia with squamous epithelium, Cell. Microbiol, vol.4, pp.73-86, 2002.

M. S. Saldías and M. A. Valvano, Interactions of Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria with epithelial and phagocytic cells, Microbiology, vol.155, pp.2809-2817, 2009.

M. S. Saldías, J. Lamothe, R. Wu, and M. A. Valvano, Burkholderia cenocepacia requires the RpoN sigma factor for biofilm formation and intracellular trafficking within macrophages, Infect. Immun, vol.76, pp.1059-1067, 2008.

J. L. Sanders, Y. Zhou, H. M. Moulton, Z. X. Moulton, R. Mcleod et al., The zebrafish, Danio rerio, as a model for Toxoplasma gondii: an initial description of infection in fish, J. Fish Dis, vol.38, issue.7, pp.675-684, 2015.

K. Sandvig, S. Pust, T. Skotland, and B. Van-deurs, Clathrin-independent endocytosis: mechanisms and function, Curr. Opin. Cell Biol, vol.23, pp.413-420, 2011.

A. M. Sar, . Van-der, R. J. Musters, F. J. Eeden, . Van et al., Zebrafish embryos as a model host for the real time analysis of Salmonella typhimurium infections, Cell. Microbiol, vol.5, pp.601-611, 2003.

C. L. Schmerk and M. Valvano, Burkholderia multivorans survival and trafficking within macrophages, J. Med. Microbiol, vol.62, issue.2, pp.173-84, 2012.

U. Schwab, M. Leigh, C. Ribeiro, J. Yankaskas, K. Burns et al., Patterns of epithelial cell invasion by different species of the Burkholderia cepacia complex in well-differentiated human airway epithelia, Infect. Immun, vol.70, pp.4547-4555, 2002.

U. Schwab, L. H. Abdullah, O. S. Perlmutt, D. Albert, C. W. Davis et al., Localization of Burkholderia cepacia complex bacteria in cystic fibrosis lungs and interactions with Pseudomonas aeruginosa in hypoxic mucus, Infect. Immun, vol.82, pp.4729-4745, 2014.

K. D. Seed and J. J. Dennis, Development of Galleria mellonella as an alternative infection model for the Burkholderia cepacia complex, Infect. Immun, vol.76, pp.1267-1275, 2008.

M. P. Sepulcre, F. Alcaraz-pérez, A. López-muñoz, F. J. Roca, J. Meseguer et al., Evolution of lipopolysaccharide (LPS) recognition and signaling: fish TLR4 does not recognize LPS and negatively regulates NF-kappaB activation, J. Immunol, vol.182, 2009.

H. Shimomura, M. Matsuura, S. Saito, Y. Hirai, Y. Isshiki et al., , 2001.

, Lipopolysaccharide of Burkholderia cepacia and its unique character to stimulate murine macrophages with relative lack of interleukin-1beta-inducing ability, Infect. Immun, vol.69, pp.3663-3669

L. M. Smith and R. C. May, Mechanisms of microbial escape from phagocyte killing, Biochem. Soc. Trans, vol.41, pp.475-490, 2013.

W. Smith, J. Green, C. E. Eden, and M. L. Watson, Nitric oxide-induced potentiation of the killing of Burkholderia cepacia by reactive oxygen species: implications for cystic fibrosis, J. Med. Microbiol, vol.48, pp.419-423, 1999.

P. A. Sokol, P. Darling, D. E. Woods, E. Mahenthiralingam, and C. Kooi, Role of ornibactin biosynthesis in the virulence of Burkholderia cepacia: characterization of pvdA, the gene encoding Lornithine N(5)-oxygenase, Infect. Immun, vol.67, pp.4443-4455, 1999.

P. A. Sokol, U. Sajjan, M. B. Visser, S. Gingues, J. Forstner et al., The CepIR quorumsensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections, Microbiology, vol.149, pp.3649-3658, 2003.

S. A. Sousa, M. Ulrich, A. Bragonzi, M. Burke, D. Worlitzsch et al., Virulence of Burkholderia cepacia complex strains in gp91phox-/-mice, Cell. Microbiol, vol.9, pp.2817-2825, 2007.

A. De-soyza, C. D. Ellis, C. M. Khan, P. A. Corris, and R. Demarco-de-hormaeche, , 2004.

, Burkholderia cenocepacia lipopolysaccharide, lipid A, and proinflammatory activity, Am. J. Respir. Crit. Care Med, vol.170, pp.70-77

H. P. Spaink, C. Cui, M. I. Wiweger, H. J. Jansen, W. J. Veneman et al., Robotic injection of zebrafish embryos for highthroughput screening in disease models, Methods, vol.62, pp.246-254, 2013.

D. P. Speert, M. Bond, R. C. Woodman, and J. T. Curnutte, Infection with Pseudomonas cepacia in chronic granulomatous disease: role of nonoxidative killing by neutrophils in host defense, J. Infect. Dis, vol.170, pp.1524-1531, 1994.

D. L. Stachura, T. , and D. , Cellular dissection of zebrafish hematopoiesis, 2011.

O. W. Stockhammer, A. Zakrzewska, Z. Hegedûs, H. P. Spaink, and A. H. Meijer, , 2009.

, Transcriptome profiling and functional analyses of the zebrafish embryonic innate immune response to Salmonella infection, J. Immunol, vol.182, pp.5641-5653

S. Subramoni and P. A. Sokol, Quorum sensing systems influence Burkholderia cenocepacia virulence, Future Microbiol, vol.7, pp.1373-1387, 2012.

C. Sullivan and C. H. Kim, Zebrafish as a model for infectious disease and immune function, Fish Shellfish Immunol, vol.25, pp.341-350, 2008.

C. Sullivan, J. Charette, J. Catchen, C. R. Lage, G. Giasson et al., The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions, J. Immunol, vol.183, pp.5896-5908, 2009.

J. L. Tan and L. I. Zon, Chemical screening in zebrafish for novel biological and therapeutic discovery, Methods Cell Biol, vol.105, pp.493-516, 2011.

M. P. Thomas, J. Whangbo, G. Mccrossan, A. J. Deutsch, K. Martinod et al., Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins, J. Immunol, vol.192, pp.5390-5397, 2014.

E. L. Thomson and J. J. Dennis, Common duckweed (Lemna minor) is a versatile highthroughput infection model for the Burkholderia cepacia complex and other pathogenic bacteria, 2013.

D. M. Tobin, R. C. May, and R. T. Wheeler, Zebrafish: a see-through host and a fluorescent toolbox to probe host-pathogen interaction, PLoS Pathog, vol.8, p.1002349, 2012.

M. Tomich, C. A. Herfst, J. W. Golden, and C. D. Mohr, Role of flagella in host cell invasion by Burkholderia cepacia, Infect. Immun, vol.70, pp.1799-1806, 2002.

M. Tomich, A. Griffith, C. A. Herfst, L. Jane, C. D. Mohr et al., Attenuated virulence of a Burkholderia cepacia Type III Secretion mutant in a murine model of infection, Infect. Immun, vol.71, issue.3, pp.1405-1415, 2003.

V. Torraca, S. Masud, H. P. Spaink, and A. H. Meijer, Macrophage-pathogen interactions in infectious diseases: new therapeutic insights from the zebrafish host model, Dis. Model. Mech, vol.7, pp.785-797, 2014.

N. S. Trede, D. M. Langenau, D. Traver, A. T. Look, and L. I. Zon, The use of zebrafish to understand immunity, Immunity, vol.20, pp.367-379, 2004.

S. Uehlinger, S. Schwager, S. P. Bernier, K. Riedel, D. T. Nguyen et al., Identification of specific and universal virulence factors in Burkholderia cenocepacia strains by using multiple infection hosts, Infect. Immun, vol.77, pp.4102-4110, 2009.

D. M. Underhill and H. S. Goodridge, Information processing during phagocytosis, Nat. Rev. Immunol, vol.12, pp.492-502, 2012.

T. A. Urban, A. Griffith, A. M. Torok, M. E. Smolkin, J. L. Burns et al., Contribution of Burkholderia cenocepacia flagella to infectivity and inflammation, Infect. Immun, vol.72, pp.5126-5134, 2004.

M. Van-der-vaart, H. P. Spaink, A. H. Meijer, M. Van-der-vaart, J. J. Van-soest et al., Functional analysis of a zebrafish myd88 mutant identifies key transcriptional components of the innate immune system, Dis. Model. Mech, vol.6, pp.841-854, 2012.

M. Van-der-vaart, C. J. Korbee, G. E. Lamers, A. C. Tengeler, R. Hosseini et al., The DNA damage-regulated autophagy modulator DRAM1 links mycobacterial recognition via TLP-MYD88 to authophagic defense, Cell Host Microbe, vol.15, pp.753-767, 2014.

E. Vanlaere, A. Baldwin, D. Gevers, D. Henry, E. De-brandt et al., Taxon K, a complex within the Burkholderia cepacia complex, comprises at least two novel species, Burkholderia contaminans sp. nov. and Burkholderia lata sp. nov, Int. J. Syst. Evol. Microbiol, vol.59, pp.102-111, 2009.

W. J. Veneman, O. W. Stockhammer, L. De-boer, S. Zaat, A. H. Meijer et al., A zebrafish high throughput screening system used for Staphylococcus epidermidis infection marker discovery, BMC Genomics, vol.14, p.255, 2013.

G. M. Ventura, V. Balloy, R. Ramphal, H. Khun, M. Huerre et al., Lack of MyD88 protects the immunodeficient host against fatal lung inflammation triggered by the opportunistic bacteria Burkholderia cenocepacia, J. Immunol, vol.183, pp.670-676, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00591436

A. C. Vergunst, A. H. Meijer, S. Renshaw, O. 'callaghan, and D. , Burkholderia cenocepacia creates an intramacrophage replication niche in zebrafish embryos, followed by bacterial dissemination and establishment of systemic infection, Infect. Immun, vol.78, pp.1495-1508, 2010.
URL : https://hal.archives-ouvertes.fr/hal-02381194

R. R. Vethanayagam, N. G. Almyroudis, M. J. Grimm, D. C. Lewandowski, C. T. Pham et al., Role of NADPH oxidase versus neutrophil proteases in antimicrobial host defense, PLoS One, vol.6, 2011.

L. Vial, A. Chapalain, M. Groleau, and E. Déziel, The various lifestyles of the Burkholderia cepacia complex species: a tribute to adaptation, Environ. Microbiol, vol.13, pp.1-12, 2011.
URL : https://hal.archives-ouvertes.fr/pasteur-00722215

A. Vural and J. H. Kehrl, Autophagy in macrophages: iImpacting inflammation and bacterial infection, Scientifica (Cairo), vol.2014, pp.1-13, 2014.

Z. Wang, S. Zhang, Z. Tong, L. Li, W. et al., Maternal transfer and protective role of the alternative complement components in zebrafish Danio rerio, PLoS One, vol.4, p.4498, 2009.

V. Wittamer, J. Y. Bertrand, P. W. Gutschow, T. , and D. , Characterization of the mononuclear phagocyte system in zebrafish, Blood, vol.117, pp.7126-7135, 2011.

C. Wright, R. Pilkington, M. Callaghan, and S. Mcclean, Activation of MMP-9 by human lung epithelial cells in response to the cystic fibrosis-associated pathogen Burkholderia cenocepacia reduced wound healing in vitro, 2011.

H. Yang, Y. Zhou, J. Gu, S. Xie, Y. Xu et al., Deep mRNA sequencing analysis to capture the transcriptome landscape of zebrafish embryos and larvae, PLoS One, vol.8, p.64058, 2013.

D. Yeh, Y. Liu, Y. Lo, C. Yuh, G. Yu et al., Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish, Proc. Natl. Acad. Sci. U. S. A, vol.110, pp.20711-20716, 2013.

D. S. Yohalem and J. W. Lorbeer, Intraspecific metabolic diversity among strains of Burkholderia cepacia isolated from decayed onions, soils, and the clinical environment, Antonie Van Leeuwenhoek, vol.65, pp.111-131, 1994.

D. Yoo, M. Floyd, M. Winn, S. M. Moskowitz, and B. Rada, NET formation induced by Pseudomonas aeruginosa cystic fibrosis isolates measured as release of myeloperoxidase-DNA and neutrophil elastase-DNA complexes, Immunol. Lett, vol.160, pp.186-194, 2014.

D. Yoo, M. Winn, L. Pang, S. M. Moskowitz, H. L. Malech et al., Release of cystic fibrosis airway inflammatory markers from Pseudomonas aeruginosa-stimulated human neutrophils involves NADPH oxidase-dependent extracellular DNA trap formation, J. Immunol, vol.192, pp.4728-4738, 2014.

Y. Yoshikawa, M. Ogawa, T. Hain, M. Yoshida, M. Fukumatsu et al., Listeria monocytogenes ActA-mediated escape from autophagic recognition, Nat. Cell Biol, vol.11, pp.1233-1240, 2009.

M. Zawrotniak and M. Rapala-kozik, Neutrophil extracellular traps (NETs) -formation and implications, Acta Biochim. Pol, vol.60, pp.277-284, 2013.

S. Zhang and P. Cui, Complement system in zebrafish, Dev. Comp. Immunol, 2014.

Z. Zhang, W. Reenstra, D. J. Weiner, J. Louboutin, and J. M. Wilson, The p38 mitogenactivated protein kinase signaling pathway is coupled to Toll-like receptor 5 to mediate gene 276 regulation in response to Pseudomonas aeruginosa infection in human airway epithelial cells, Infect. Immun, vol.75, pp.5985-5992, 2007.

Y. Zhong, A. Kinio, and M. Saleh, Functions of NOD-Like Receptors in Human Diseases, 2013.

, Nous avons montré que B. cenocepacia K56-2 pouvait se répliquer dans les macrophages et causer une infection aiguë mortelle pour les embryons. En revanche, B. stabilis LMG14294 induit une infection persistante chez les embryons. Dans cette étude, nous avons montré que les macrophages jouaient un rôle-clé dans la multiplication de K56-2 et dans l'induction d'une réponse inflammatoire MyD88-dépendante, caractérisée par la surexpression des gènes codant pour Cxcl8 (ou IL-8) et l'IL-1b. En l'absence de macrophages, les bactéries sont incapables de se multiplier durant les premières 24h de l'infection, ce qui donne un avantage pour la survie des embryons. L'absence de MyD88 induit aussi l'augmentation de la survie des embryons infectés par K56-2. Mais de manière paradoxale, les bactéries se multiplient mieux chez les embryons myd88 -/-mutants que chez les embryons sauvages. Ceci suggère que ce n'est pas le nombre de bactéries qui est important pour l'infection, mais que c'est la réponse inflammatoire excessive causée par cette infection qui entraîne la mort des embryons. Afin d'avoir une vision globale des changements d'expression des gènes de l'hôte durant l'infection, nous avons effectué une expérience de RNAseq. Comme attendu, l'infection aiguë se caractérise par une importante modulation du transcriptome de l'hôte qui augmente avec le temps. A l'opposé, l'infection persistante n'induit que très peu de changements. La réponse immunitaire innée, Les bactéries appartenant au complexe Burkholderia cepacia (Bcc) provoquent des infections sévères chez les personnes atteintes de mucoviscidose. L'infection peut varier d'une forme asymptomatique à une forme plus aiguë pouvant entraîner une pneumonie nécrosante et une septicémie, connue sous le nom de syndrome cepacia

, Le rôle critique des macrophages lors d'une infection par Bcc chez les poissons zèbre est en accord avec les récentes observations cliniques. Ceci suggère que le stade intracellulaire de B. cenocepacia et la réponse inflammatoire qui s'ensuit peuvent être des cibles pour le développement de nouvelles thérapies permettant de lutter contre cette infection. Mots clés : Burkholderia cenocepacia