NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice
- Author(s)
- 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;
- Details
- Publication Year 2023-06-26,Volume 14,Issue #1,Page 3804
- Journal Title
- Nature Communications
- 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.
- Publisher
- NPG
- Research Division(s)
- Ubiquitin Signalling; Inflammation
- PubMed ID
- 37365163
- Publisher's Version
- https://doi.org/10.1038/s41467-023-39487-1
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-023-39487-1- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-30 02:16:25
Last Modified: 2023-06-30 03:08:49