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Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.

Nature | Jun 29, 2017

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens.

Pubmed ID: 28636595 RIS Download

Mesh terms: Animals | Apoptosis Regulatory Proteins | CARD Signaling Adaptor Proteins | Caspase 1 | DEAD-box RNA Helicases | Epithelial Cells | Female | Immunity, Innate | Inflammasomes | Interleukin-18 | Intestines | Male | Mice | Mice, Inbred C57BL | Pyroptosis | RNA, Double-Stranded | Receptors, G-Protein-Coupled | Rotavirus | Rotavirus Infections

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Associated grants

  • Agency: NIAID NIH HHS, Id: R21 AI103807
  • Agency: NIAID NIH HHS, Id: T32 AI007019
  • Agency: NCATS NIH HHS, Id: UL1 TR001863
  • Agency: NIAID NIH HHS, Id: R01 AI021362
  • Agency: Howard Hughes Medical Institute, Id: R01 DK099097
  • Agency: NIDDK NIH HHS, Id: U19 AI089992
  • Agency: NIAID NIH HHS, Id: I01 BX000158
  • Agency: BLRD VA, Id: R01 DK106593
  • Agency: NIDDK NIH HHS, Id: U19 AI116484
  • Agency: NIAID NIH HHS, Id: R56 AI021362
  • Agency: NIAID NIH HHS, Id: R01 AI125249
  • Agency: NIAID NIH HHS, Id: R01 AI120369
  • Agency: NIAID NIH HHS, Id:

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