Rotavirus is a leading cause of severe diarrhoea in children but how host intestinal epithelial cells (IEC) detect and respond to rotaviral infections remains unresolved. Inflammasome activation often promotes host defence mechanisms and Zhu et al. observed increased caspase-1 activity (indicative of inflammasome activation) in suckling pups inoculated with mouse rotavirus. Investigating sensor proteins, the researchers focused on NOD-like receptor (NLR) inflammasomes and found that global or IEC-specific deletion in mice of NLRP9B, an uncharacterized NLR, resulted in increased susceptibility to rotavirus infection, suggesting an important role for this protein in protecting against intestinal infection. Furthermore, the investigators determined that NLRP9B responds to rotaviral double-stranded RNA via the RNA helicase DHX9, forming an inflammasome complex that promotes IL-18 immune responses and gasdermin D-mediated pyroptosis of IECs to limit infection. Targeting the IEC-specific NLRP9B might facilitate the development of novel therapeutics for this infectious disease.
Zhu, S. et al. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature http://dx.doi.org/10.1038/nature22967 (2017)
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Dickson, I. Inflammasome modulates rotavirus infection. Nat Rev Gastroenterol Hepatol 14, 450 (2017). https://doi.org/10.1038/nrgastro.2017.94