Abstract
Natural interferon-producing cells (IPCs) specialize in the production of high levels of type 1 interferons (IFNs) in response to encapsulated DNA and RNA viruses. Here we demonstrate that the secretion of type 1 IFN in response to herpes simplex virus type 1 (HSV-1) in vitro is mediated by the toll-like receptor 9 (TLR9)/MyD88 pathway. Moreover, IPCs produce interleukin-12 (IL-12) in response to HSV-1 in vitro, which is also dependent on TLR9/ MyD88 signaling. Remarkably, though TLR9/MyD88-deficiency abrogates IPC responses to HSV-1 in vitro, mice lacking either MyD88 or TLR9 are capable of controlling HSV-1 replication in vivo after local infection, demonstrating that TLR9- and MyD88-independent pathways in cells other than IPCs can effectively compensate for defective IPC responses to HSV-1.
Publication types
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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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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, Differentiation / genetics
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Antiviral Agents / pharmacology
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DNA-Binding Proteins / immunology*
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DNA-Binding Proteins / metabolism*
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Herpes Simplex / drug therapy
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Herpes Simplex / immunology*
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Herpesvirus 1, Human / growth & development
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Herpesvirus 1, Human / immunology*
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Interferon-alpha / pharmacology
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Interleukin-12 / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Myeloid Differentiation Factor 88
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / metabolism*
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Receptors, Immunologic / genetics
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Toll-Like Receptor 9
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Virus Replication / immunology
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Antiviral Agents
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DNA-Binding Proteins
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Interferon-alpha
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MYD88 protein, human
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Cell Surface
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Receptors, Immunologic
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Tlr9 protein, mouse
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Toll-Like Receptor 9
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Interleukin-12