Nlrp6 regulates intestinal antiviral innate immunity.
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.
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
Penghua
P
Wang
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Shu
S
Zhu
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
Long
L
Yang
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Shuang
S
Cui
Department of Genetics, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Wen
W
Pan
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Ruaidhri
R
Jackson
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Yunjiang
Y
Zheng
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Anthony
A
Rongvaux
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Qiangming
Q
Sun
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Guang
G
Yang
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Shandian
S
Gao
Lady Davis Institute, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Rongtuan
R
Lin
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA.
Fuping
F
You
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA. richard.flavell@yale.edu erol.fikrig@yale.edu.
Richard
R
Flavell
Section of Infectious Diseases, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA. richard.flavell@yale.edu erol.fikrig@yale.edu.
Erol
E
Fikrig
D000818:Animals; D017250:Caliciviridae Infections / Q000276:immunology / Q000821:virology; D018188:Cardiovirus Infections / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000235:genetics; D004686:Encephalomyocarditis virus / Q000276:immunology; D005759:Gastroenteritis / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007370:Interferon Type I / Q000276:immunology*; D007422:Intestines / Q000276:immunology* / Q000821:virology*; D051379:Mice; D008817:Mice, Mutant Strains; D029322:Norovirus / Q000276:immunology; D020365:RNA Helicases / Q000502:physiology*; D012367:RNA, Viral / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D014452:Ubiquitins / Q000235:genetics; D014766:Viremia / Q000235:genetics / Q000276:immunology
D016207:Cytokines; C489550:G1p2 protein, mouse; D007370:Interferon Type I; C559901:Nod-like receptor pyrin domain-containing protein 6, mouse; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D014452:Ubiquitins; C000603338:Dhx15 protein, mouse; D020365:RNA Helicases