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Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses

Blanchet, Fabien, Moris, Arnaud, Nikolic, Damjan S., Lehmann, Martin, Cardinaud, Sylvain, Stalder, Romaine, Garcia, Eduardo, Dinkins, Christina, Leuba, Florence, Wu, Li, Schwartz, Olivier, Deretic, Vojo and Piguet, Vincent 2010. Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity 32 (5) , pp. 654-669. 10.1016/j.immuni.2010.04.011

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Uncontrolled Keywords: Molimmuno; microbio; cellbio
Publisher: Elsevier
ISSN: 1074-7613
Last Modified: 04 Jun 2017 04:21
URI: http://orca.cf.ac.uk/id/eprint/37359

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