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

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

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.

PMID:
21844166
PMCID:
PMC3177694
DOI:
10.1189/jlb.0311166
[Indexed for MEDLINE]
Free PMC Article

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