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Human Immunodeficiency Virus-1 Inhibition of Immunoamphisomes in Dendritic Cells Impairs Early Innate and Adaptive Immune Responses.

Abstract : Dendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter. However, immune response in the early events of HIV-1 transmission appears limited, suggesting that HIV-1 evade early immune control by DCs. We report that HIV-1 induces a rapid shutdown of autophagy and immunoamphisomes in DCs. HIV-1 envelope activated the mammalian target of rapamycin pathway in DCs, leading to autophagy exhaustion. HIV-1-induced inhibition of autophagy in DC increased cell-associated HIV-1 and transfer of HIV-1 infection to CD4(+) T cells. HIV-1-mediated downregulation of autophagy in DCs impaired innate and adaptive immune responses. Immunoamphisomes in DCs engulf incoming pathogens and appear to amplify pathogen degradation as well as Toll-like receptor responses and antigen presentation. The findings that HIV-1 downregulates autophagy and impedes immune functions of DCs represent a pathogenesis mechanism that can be pharmacologically countered with therapeutic and prophylactic implications.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00488629
Contributor : Mireille Gau <>
Submitted on : Wednesday, June 2, 2010 - 11:45:34 AM
Last modification on : Monday, January 13, 2020 - 5:08:10 PM

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Fabien P Blanchet, Arnaud Moris, Damjan S Nikolic, Martin Lehmann, Sylvain Cardinaud, et al.. Human Immunodeficiency Virus-1 Inhibition of Immunoamphisomes in Dendritic Cells Impairs Early Innate and Adaptive Immune Responses.. Immunity, Elsevier, 2010, 32 (5), pp.654-669. ⟨10.1016/j.immuni.2010.04.011⟩. ⟨pasteur-00488629⟩

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