RRC ID 76457
Author Tran LS, Ying L, D'Costa K, Wray-McCann G, Kerr G, Le L, Allison CC, Ferrand J, Chaudhry H, Emery J, De Paoli A, Colon N, Creed S, Kaparakis-Liaskos M, Como J, Dowling JK, Johanesen PA, Kufer TA, Pedersen JS, Mansell A, Philpott DJ, Elgass KD, Abud HE, Nachbur U, Croker BA, Masters SL, Ferrero RL.
Title NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice.
Journal Nat Commun
Abstract 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.
Volume 14(1)
Pages 3804
Published 2023-6-26
DOI 10.1038/s41467-023-39487-1
PII 10.1038/s41467-023-39487-1
PMID 37365163
PMC PMC10293252
MeSH Animals Epithelial Cells* / metabolism Helicobacter Infections* / metabolism Helicobacter pylori Inflammasomes / metabolism Interleukin-18* / metabolism Interleukin-1beta / metabolism Mice NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Nod1 Signaling Adaptor Protein* / metabolism Signal Transduction
IF 12.121
Human and Animal Cells GSM06(RCB1779)