Contributors: Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Institut Pasteur Paris (IP); HIV, Inflammation et persistance - HIV, Inflammation and Persistence; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); This work was supported by the “Programme Investissements d’Avenir” (PIA), managed by the ANR under reference ANR-11-INBS-0008, funding the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure, and ANR-10-EQPX-02-01, funding the FlowCyTech facility (IDMIT, Fontenay-aux-Roses, France). We thank Gilead and ViiV for providing the antiretroviral drugs. Animal studies were supported by the ANRS and MSD Avenir, as part of the ANRS RHIVIERA pVISCONTI research program, and the SIVART ANRS-IDMIT CO1 research program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We thank C. Joubert, R. Ho Tsong Fang, B. Delache, S. Langlois, J. Demilly, N. Dhooge, P. Le Calvez, M. Potier, F. Relouzat, J. M. Robert, T. Prot and C. Dodan for the NHP experiments; Jérôme Van Wassenhove and Wesley Gros for flow cytometry staining, L. Bossevot, M. Leonec, L. Moenne-Loccoz and J. Morin for the RT-qPCR assays, and for the preparation of reagents; M. Barendji, J. Dinh and E. Guyon for the NHP sample processing; S. Keyser for the transports organization; N. Dimant and B. Targat for their help with the experimental studies; F. Ducancel and Y. Gorin for their help with the logistics and safety management; I. Mangeot for here help with resources management. We thank G. Carvalho, J. Mafille, and S. Mouhamad from Miltenyi Biotech for their help on panel design and cell sorting; V. Witko-Sarsat from Cochin institute for her help and outstanding expertise on neutrophils; P. Delobel from CPTP for his advice and thorough previewing of the manuscript.; ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011)
نبذة مختصرة : International audience ; In spite of the efficacy of combinational antiretroviral treatment (cART), HIV-1 persists in the host and infection is associated with chronic inflammation, leading to an increased risk of comorbidities, such as cardiovascular diseases, neurocognitive disorders, and cancer. Myeloid cells, mainly monocytes and macrophages, have been shown to be involved in the immune activation observed in HIV-1 infection. However, less attention has been paid to neutrophils, the most abundant circulating myeloid cell, even though neutrophils are strongly involved in tissue damage and inflammation in several chronic diseases, in particular, autoimmune diseases. Herein, we performed a longitudinal characterization of neutrophil phenotype and we evaluated the interplay between neutrophils and T cells in the model of pathogenic SIVmac251 experimental infection of cynomolgus macaques. We report that circulating granulocytes consists mainly of immature CD10- neutrophils exhibiting a prime phenotype during primary and chronic infection. We found that neutrophil priming correlates with CD8 + T cell activation. Moreover, we provide the evidence that neutrophils are capable of modulating CD4 + and CD8 + T-cell proliferation and IFN-γ production in different ways depending on the time of infection. Thus, our study emphasizes the role of primed immature neutrophils in the modulation of T-cell responses in SIV infection.
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