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Heterogeneity of polymorphonuclear neutrophils in HIV-1 infection. Study of SIV-infected cynomolgus macaque model.

Abstract : Even under combinational antiretroviral treatments (cART), HIV-1 persistence is associated with chronic inflammation in infected patients, leading to an increased risk of non-AIDS-related comorbidities. Polymorphonuclear neutrophils (PMN), have been less studied in HIV infection whereas they were associated with chronic inflammation diseases. To evaluate PMN heterogeneity in SIVmac251 nonhuman primate infection model, we first performed multiparameter single-cell phenotyping by mass cytometry giving a global vision of the immune system. This analysis demonstrated circulation of immature PMN with impaired during chronic infection. Then, we characterized neutrophils heterogeneity in the course of SIV infection. In primary infection, there was an increased frequency of CD10- immature and CD62L-low primed PMNs in peripheral blood. In chronic phase, CD10- immature PMNs were significantly higher in bone marrow and blood, maintaining a primed profile. During SIV infection, PMNs demonstrated variable immunomodulatory function against T cells proliferation and cytokine production. Early cART allowed to restore PMN phenotype. In this study, we provide unprecedented insight into PMN heterogeneity in the course of SIV infection. Since PMN represent 40-70% of circulating leukocytes and primed PMN are more potent to release pro-inflammatory cytokines and to transmigrate, they should be considered as a new player in HIV-1 chronic inflammation.
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Julien Lemaitre. Heterogeneity of polymorphonuclear neutrophils in HIV-1 infection. Study of SIV-infected cynomolgus macaque model.. Innate immunity. Université Paris Saclay (COmUE), 2019. English. ⟨NNT : 2019SACLS267⟩. ⟨tel-02955513⟩

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