Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection.
Plasmacytoid dendritic cells (pDC) are the principal producers of IFN-alpha in response to viral infection. Because pDC are present in the thymus, we investigated the consequences of HIV-1-induced IFN-alpha production by thymic pDC. We observed that thymic pDC as well as thymocytes express intracellular IFN-alpha upon infection with HIV-1. However, only the pDC could suppress HIV-1 replication, because depletion of pDC resulted in enhancement of HIV-1 replication in thymocytes. Thymic pDC could also produce IFN-alpha in response to CpG oligonucleotides, consistent with the observations of others that peripheral pDC produce IFN-alpha upon engagement of TLR-9. Importantly, CpG considerably increased IFN-alpha production induced by HIV-1, and addition of CpG during HIV-1 infection enhanced expression of the IFN response protein MxA in thymocytes and strongly reduced HIV-replication. Our data indicate that thymic pDC modulate HIV-1 replication through secretion of IFN-alpha. The degree of inhibition depends on the level of IFN-alpha produced by the thymic pDC.
Gurney
Kevin B
KB
Department of Microbiology, Immunology, and Molecular Genetics, David E. Geffen School of Medicine, University of California, Los Angeles CA 90095, USA.
Colantonio
Arnaud D
AD
Blom
Bianca
B
Spits
Hergen
H
Uittenbogaart
Christel H
CH
D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002648:Child; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D064547:Myxovirus Resistance Proteins; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009924:Organ Culture Techniques; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000637:transplantation / Q000821:virology*; D015854:Up-Regulation / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; C408982:CPG-oligonucleotide; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D009838:Oligodeoxyribonucleotides; D019204:GTP-Binding Proteins