Nature Communications · 2023 · 23 citations · 56 references
Veterinary MedicineImmunologyInfectious DiseasesHost-pathogen InteractionsInflammationInnate ImmunityCytokine BiologyGastrointestinal InflammationInflammasome ActivationInflammation In Infectious DiseaseInnate Immune Signaling PathwaysMucosal InflammationEpithelial Cell ResponseHelicobacter Pylori InfectionHelicobacter Pylori PathogenesisInterleukin-1 Beta MaturationInterleukin-1 Family CytokinesInterleukin-18 ProcessingNod1 SignalingProtein Complexes
The interleukin-1 family members, IL-1β and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1β processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.
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