| Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. | |
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MedLine Citation:
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PMID: 20451412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Fabien P Blanchet; Arnaud Moris; Damjan S Nikolic; Martin Lehmann; Sylvain Cardinaud; Romaine Stalder; Eduardo Garcia; Christina Dinkins; Florence Leuba; Li Wu; Olivier Schwartz; Vojo Deretic; Vincent Piguet |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-06 |
Journal Detail:
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Title: Immunity Volume: 32 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-06-21 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 654-69 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Dermatology, University Hospital and Medical School of Geneva, 1211 Geneva, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI068493-05/AI/NIAID NIH HHS; R01 AI068493-06/AI/NIAID NIH HHS; R01-AI068493/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Intracellular Signaling Peptides and Proteins; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.37/ribosomal protein S6 kinase, 70kD, polypeptide 1; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa |
| Comments/Corrections | |
Comment In:
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Immunity. 2010 May 28;32(5):587-90
[PMID:
20510868
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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