Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-HIV Agents / metabolism*
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Antibodies, Monoclonal / pharmacology
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Child
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CpG Islands / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Dendritic Cells / virology
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GTP-Binding Proteins / biosynthesis
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GTP-Binding Proteins / genetics
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HIV-1 / growth & development
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HIV-1 / immunology*
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Humans
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Interferon-alpha / antagonists & inhibitors
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Interferon-alpha / biosynthesis*
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Interferon-alpha / immunology*
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Interferon-alpha / metabolism
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Liver Transplantation / immunology
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Lymphocyte Subsets / immunology
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Lymphocyte Subsets / virology
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Mice
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Mice, SCID
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Myxovirus Resistance Proteins
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Neutralization Tests
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Oligodeoxyribonucleotides / pharmacology
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Organ Culture Techniques
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Thymus Gland / cytology
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Thymus Gland / immunology*
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Thymus Gland / transplantation
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Thymus Gland / virology*
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Up-Regulation / immunology
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Virus Replication / immunology
Substances
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Anti-HIV Agents
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Antibodies, Monoclonal
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CPG-oligonucleotide
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Interferon-alpha
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MX1 protein, human
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Myxovirus Resistance Proteins
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Oligodeoxyribonucleotides
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GTP-Binding Proteins