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Theses

LES EOSINOPHILES : EFFECTEURS DE LA REPONSE IMMUNITAIRE INNEE ANTI-MYCOBACTERIENNE

Abstract : Eosinophils are multifunctional leukocytes involved in various inflammatory processes. Recent studies provide evidence that eosinophils can exert different functions through their ability to express different receptors and to produce both Th1- and Th2-type cytokines upon stimulation. The role of eosinophils in mycobacterial pathogenesis is still not well defined. Recently, an accumulation of eosinophils within lung granuloma was reported in different models of mycobacterial infections, while a lytic activity against M. tuberculosis was assigned to eosinophil peroxydase (EPO). The aims of this study were to demonstrate a direct interaction of human eosinophils with mycobacteria and to analyse the mechanisms involved.
We demonstrate that M. bovis BCG attracts and activates eosinophils in vitro. Indeed, eosinophils produce Reactive Oxygen Species (ROS) and release EPO in the presence of BCG. We report here that only TLR2, but not TLR4 is involved in eosinophil/ BCG interactions through activation of MAP kinase and NF-κB signalling pathways. Finally, we show that eosinophils can exert cytotoxic functions against BCG through production of defensins. Because eosinophils express various surface receptors shared with Tcells such as CD25, CD4, CD28 and several members of the CD2 family, including 2B4, we have studied other receptors could involved in eosinophil/M. bovis BCG interactions. Here we show, by flow cytometry, immunofluorescence and confocal microscopy that a variable proportion of human eosinophils express CD3 and gamma delta T Cell Receptor (TCR). Moreover, gamma deltaTCR/CD3 is involved in activation of eosinophils with Mycobacterium.
This work represents the first demonstration of a direct interaction between human eosinophils and M. bovis-BCG and suggests a novel role for eosinophils in TLR2-and CD3/γδTCR mediated innate immunity. Furthermore, defensins act as a novel cytotoxic pathway for eosinophils. In conclusion, these results suggest that eosinophils interact with danger signals including mycobacteria, and are a link between innate and adaptive immunity.
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Contributor : Virginie Driss <>
Submitted on : Tuesday, March 24, 2009 - 9:57:32 AM
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Virginie Driss. LES EOSINOPHILES : EFFECTEURS DE LA REPONSE IMMUNITAIRE INNEE ANTI-MYCOBACTERIENNE. Immunologie. Université du Droit et de la Santé - Lille II, 2008. Français. ⟨tel-00370300⟩

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