Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9.
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.
Krug
Anne
A
Department of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA.
Luker
Gary D
GD
Barchet
Winfried
W
Leib
David A
DA
Akira
Shizuo
S
Colonna
Marco
M
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
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