PMID- 20451412 OWN - NLM STAT- MEDLINE DCOM- 20100621 LR - 20230815 IS - 1097-4180 (Electronic) IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 32 IP - 5 DP - 2010 May 28 TI - Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. PG - 654-69 LID - 10.1016/j.immuni.2010.04.011 [doi] AB - 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. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Blanchet, Fabien P AU - Blanchet FP AD - Department of Dermatology, University Hospital and Medical School of Geneva, 1211 Geneva, Switzerland. FAU - Moris, Arnaud AU - Moris A FAU - Nikolic, Damjan S AU - Nikolic DS FAU - Lehmann, Martin AU - Lehmann M FAU - Cardinaud, Sylvain AU - Cardinaud S FAU - Stalder, Romaine AU - Stalder R FAU - Garcia, Eduardo AU - Garcia E FAU - Dinkins, Christina AU - Dinkins C FAU - Leuba, Florence AU - Leuba F FAU - Wu, Li AU - Wu L FAU - Schwartz, Olivier AU - Schwartz O FAU - Deretic, Vojo AU - Deretic V FAU - Piguet, Vincent AU - Piguet V LA - eng GR - R01 AI042999/AI/NIAID NIH HHS/United States GR - R01-AI068493/AI/NIAID NIH HHS/United States GR - R01 AI068493-06/AI/NIAID NIH HHS/United States GR - R37 AI042999/AI/NIAID NIH HHS/United States GR - R01 AI068493/AI/NIAID NIH HHS/United States GR - T32 AI007538/AI/NIAID NIH HHS/United States GR - R01 AI068493-05/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100506 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1) SB - IM CIN - Immunity. 2010 May 28;32(5):587-90. PMID: 20510868 MH - *Adaptive Immunity MH - Autophagy MH - Base Sequence MH - CD4-Positive T-Lymphocytes/virology MH - Cells, Cultured MH - Dendritic Cells/*immunology/pathology/*virology MH - Down-Regulation MH - Flow Cytometry MH - HIV Infections/*immunology MH - HIV-1/*physiology MH - Humans MH - *Immunity, Innate MH - Immunoblotting MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Lysosomes/immunology/virology MH - Molecular Sequence Data MH - Phagosomes/*immunology/virology MH - Protein Serine-Threonine Kinases/metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Signal Transduction MH - TOR Serine-Threonine Kinases PMC - PMC2929482 MID - NIHMS205642 EDAT- 2010/05/11 06:00 MHDA- 2010/06/22 06:00 PMCR- 2011/05/28 CRDT- 2010/05/11 06:00 PHST- 2009/07/09 00:00 [received] PHST- 2009/12/10 00:00 [revised] PHST- 2010/03/23 00:00 [accepted] PHST- 2010/05/11 06:00 [entrez] PHST- 2010/05/11 06:00 [pubmed] PHST- 2010/06/22 06:00 [medline] PHST- 2011/05/28 00:00 [pmc-release] AID - S1074-7613(10)00160-3 [pii] AID - 10.1016/j.immuni.2010.04.011 [doi] PST - ppublish SO - Immunity. 2010 May 28;32(5):654-69. doi: 10.1016/j.immuni.2010.04.011. Epub 2010 May 6.