Journal article
Human Immunodeficiency Virus-1 Inhibition of Immunoamphisomes in Dendritic Cells Impairs Early Innate and Adaptive Immune Responses
Immunity (Cambridge, Mass.), Vol.32(5), pp.654-669
2010
DOI: 10.1016/j.immuni.2010.04.011
PMCID: PMC2929482
PMID: 20451412
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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► HIV-1 activates mTOR pathway and induces a rapid shutdown of autophagy in DCs ► LC3
+ amphisomes can target incoming virions to lysosomal compartments ► Impaired DC-autophagy leads to increased viral content and transfer to CD4
+ T cells ► HIV-1-mediated autophagy inhibition alters DC innate and adaptive immune responses
Details
- Title: Subtitle
- Human Immunodeficiency Virus-1 Inhibition of Immunoamphisomes in Dendritic Cells Impairs Early Innate and Adaptive Immune Responses
- Creators
- Fabien P Blanchet - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, SwitzerlandArnaud Moris - Institut Pasteur, Virus and Immunity Unit, 75015 Paris, FranceDamjan S Nikolic - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, SwitzerlandMartin Lehmann - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, SwitzerlandSylvain Cardinaud - INSERM UMRS-945, UPMC, 75013 Paris, FranceRomaine Stalder - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, SwitzerlandEduardo Garcia - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, SwitzerlandChristina Dinkins - University of New-Mexico, Albuquerque, NM 87131, USAFlorence Leuba - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, SwitzerlandLi Wu - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USAOlivier Schwartz - Institut Pasteur, Virus and Immunity Unit, 75015 Paris, FranceVojo Deretic - University of New-Mexico, Albuquerque, NM 87131, USAVincent Piguet - Departments of Dermatology and Venereology, Microbiology and Molecular Medicine, University Hospital and Medical School of Geneva, 1211 Geneva, Switzerland
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.32(5), pp.654-669
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.immuni.2010.04.011
- PMID
- 20451412
- PMCID
- PMC2929482
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Language
- English
- Date published
- 2010
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002381802771
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