NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice

L. S. Tran, L. Ying, K. D’Costa, G. Wray-McCann, G. Kerr, L. Le, C. C. Allison, J. Ferrand, H. Chaudhry, J. Emery, A. De Paoli, N. Colon, S. Creed, M. Kaparakis-Liaskos, J. Como, J. K. Dowling, P. A. Johanesen, T. A. Kufer, J. S. Pedersen, A. MansellD. J. Philpott, K. D. Elgass, H. E. Abud, U. Nachbur, B. A. Croker, S. L. Masters, R. L. Ferrero

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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.

Original languageEnglish
Article number3804
Number of pages18
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2023

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