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Nlrp6 regulates intestinal antiviral innate immunity

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Science  13 Nov 2015:
Vol. 350, Issue 6262, pp. 826-830
DOI: 10.1126/science.aab3145

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Nlrp6 keeps gut infections in check

Most viruses infect only certain cells of the body. Enteric viruses, such as norovirus and rotavirus, specifically infect the gut. Wang et al. now show that the response to such viruses is tissue-specific, too. Antiviral immunity to enteric but not systemic viral infections in mice required Nlrp6, a member of the NOD-like receptor family of proteins that play important roles in host defense. Together with the RNA helicase protein Dhx15, Nlrp6 bound viral RNA and elicited downstream antiviral immune responses necessary for viral clearance. These included the production of type I and type III interferons and the expression of interferon-stimulated genes.

Science, this issue p. 826

Abstract

The nucleotide-binding oligomerization domain–like receptor (Nlrp) 6 maintains gut microbiota homeostasis and regulates antibacterial immunity. We now report a role for Nlrp6 in the control of enteric virus infection. Nlrp6−/− and control mice systemically challenged with encephalomyocarditis virus had similar mortality; however, the gastrointestinal tract of Nlrp6−/− mice exhibited increased viral loads. Nlrp6−/− mice orally infected with encephalomyocarditis virus had increased mortality and viremia compared with controls. Similar results were observed with murine norovirus 1. Nlrp6 bound viral RNA via the RNA helicase Dhx15 and interacted with mitochondrial antiviral signaling protein to induce type I/III interferons (IFNs) and IFN-stimulated genes (ISGs). These data demonstrate that Nlrp6 functions with Dhx15 as a viral RNA sensor to induce ISGs, and this effect is especially important in the intestinal tract.

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