title: Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9.
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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Krug
authors.forename: Gary D
authors.initials: GD
authors.lastname: Luker
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: David A
authors.initials: DA
authors.lastname: Leib
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism*; D006561:Herpes Simplex / Q000188:drug therapy / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000276:immunology*; D016898:Interferon-alpha / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics; D051217:Toll-Like Receptor 9; D014779:Virus Replication / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D018664:Interleukin-12