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PMID: 20451412 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Immunity ·Vol. 32 ·No. 5 ·2010-05-28 ·Pages 654-69

Blanchet FP, Moris A, Nikolic DS, Lehmann M, Cardinaud S, Stalder R, Garcia E, Dinkins C, Leuba F, Wu L, Schwartz O, Deretic V, Piguet V

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.

MeSH Terms
Adaptive Immunity Autophagy Base Sequence CD4-Positive T-Lymphocytes/virology Cells, Cultured Dendritic Cells/immunology,pathology,virology Down-Regulation Flow Cytometry HIV Infections/immunology HIV-1/physiology Humans Immunity, Innate Immunoblotting Intracellular Signaling Peptides and Proteins/metabolism Lysosomes/immunology,virology Molecular Sequence Data Phagosomes/immunology,virology Protein Serine-Threonine Kinases/metabolism Ribosomal Protein S6 Kinases, 70-kDa/metabolism Signal Transduction TOR Serine-Threonine Kinases
Chemicals
Intracellular Signaling Peptides and Proteins MTOR protein, human Protein Serine-Threonine Kinases Ribosomal Protein S6 Kinases, 70-kDa TOR Serine-Threonine Kinases ribosomal protein S6 kinase, 70kD, polypeptide 1
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Blanchet Fabien P
Department of Dermatology, University Hospital and Medical School of Geneva, 1211 Geneva, Switzerland.
Moris Arnaud
Nikolic Damjan S
Lehmann Martin
Cardinaud Sylvain
Stalder Romaine
Garcia Eduardo
Dinkins Christina
Leuba Florence
Wu Li
Schwartz Olivier
Deretic Vojo
Piguet Vincent
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2010.04.011
Published
2010-05-28
Epub
2010-00-06
Pages
654-69
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2929482
Subset
IM
Grants
NIAID NIH HHS · R01 AI042999 · United States
NIAID NIH HHS · R01-AI068493 · United States
NIAID NIH HHS · R01 AI068493-06 · United States
NIAID NIH HHS · R37 AI042999 · United States
NIAID NIH HHS · R01 AI068493 · United States
NIAID NIH HHS · T32 AI007538 · United States
NIAID NIH HHS · R01 AI068493-05 · United States
Corrections
CommentIn
PMID: 20510868
External Links
PubMed source DOI: 10.1016/j.immuni.2010.04.011 PMC Full Text View journal details
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