title: TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes.
abstract: IFN-I are pleiotropic cytokines that impact innate and adaptive immune responses. In this article, we discuss TLR7/9 versus TLR3/MDA5 signaling in antiviral responses and diabetes. pDCs are thought to have a critical role in antiviral defense because of their ability to rapidly secrete large amounts of IFN-I through TLR7/9 signaling. A recent study demonstrates that although pDCs are a source of IFN-I in vivo, their overall contribution to viral containment is limited and time-dependent, such that additional cellular sources of IFN-I are required to fully control viral infections. dsRNA sensors, such as TLR3 and MDA5, provide another important trigger for antiviral IFN-I responses, which can be exploited to enhance immune responses to vaccines. In the absence of infection, IFN-I production by pDCs or from signaling through dsRNA sensors has been implicated in the pathogenesis of autoimmune diseases such as diabetes. However, recent data demonstrate that IFN-I production via TLR3 and MDA5 is critical to counter diabetes caused by a virus with preferential tropism for pancreatic β-cells. This highlights the complexity of the host antiviral response and how multiple cellular and molecular components balance protective versus pathological responses.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Swiecki
authors.forename: Stephen A
authors.initials: SA
authors.lastname: McCartney
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wang
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1; D010950:Plasma Cells / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D012330:RNA, Double-Stranded; C495346:TLR5 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1