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    Immune activation and suppression during HIV infection

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    Principal investigator : Anne Hosmalin

    Mail : anne.hosmalin@inserm.fr

    Phone number : +33 1 40 51 65 06

     

    We study the role of different DC and monocyte/macrophage populations during HIV-1 or HIV-2 infections in the production of type I or III Interferons (IFN) and in T cell polarization. We study patient samples from cohorts from the National Agency for AIDS Research (ANRS) or from cohorts that we have set up in collaboration with the Cochin-Pasteur Clinical Investigation Center (CIC) directed by Odile Launay. We were first to show the depletion of circulating DC and the accumulation of slan+, pro-inflammatory monocytes during HIV infection. We also found that pDC home into secondary lymphoid organs, using analogy with SIV infection models, in collaboration with other laboratories.

    Combined antiretroviral treatments control plasma viral loads, prevent the occurrence of AIDS and give back to HIV-infected patients a life expectancy close to normal. However, an immune hyper-activation persists and correlates with metabolic and cardiovascular complications. Stricken by the IFN response paradox, with concurrent antiviral and pro-inflammatory effects, we wondered what was the effect of type I IFN alone on in vivo immune responses. We found that chronic exposure to low-dose IFN-a4 induced the suppression of  antiviral CD8+ T cell responses, mediated by myeloid-derived suppressive cells (MDSC).

    We are particularly interested in the anatomy of the immune response in tissue micro-environments, especially in the human spleen, and also in the central nervous system, for which we attempt to set up a new cell model.

    Our aim is to reduce reservoirs and to restore balanced immune responses against HIV.

     

    Techniques

    Our current projects rely on cellular immunology, multi-color flow cytometry and rare cell sorting, confocal microscopy, mass cytometry, single cell RNA sequencing, immunofluorescence and histology.

     

    Funding

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