TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes

J Leukoc Biol. 2011 Oct;90(4):691-701. doi: 10.1189/jlb.0311166. Epub 2011 Aug 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DEAD-box RNA Helicases / immunology*
  • Dendritic Cells / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Humans
  • Insulin-Secreting Cells / immunology
  • Interferon Type I / immunology
  • Interferon-Induced Helicase, IFIH1
  • Plasma Cells / immunology
  • RNA, Double-Stranded / immunology
  • Signal Transduction / immunology*
  • Toll-Like Receptor 5 / immunology*
  • Toll-Like Receptor 7 / immunology*
  • Toll-Like Receptor 9 / immunology*
  • Virus Diseases / immunology*


  • Interferon Type I
  • RNA, Double-Stranded
  • TLR5 protein, human
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 5
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1