NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 26, 2023
- Source ID
- 10.1038/s41467-023-39487-1
Entities
People
- A. De Paoli
- Ashley Mansell
- Ben Croker
- C. C. Allison
- Dana Philpott
- Genevieve Kerr
- Georgie Wray‐McCann
- H. Chaudhry
- Helen Abud
- J. Emery
- J. Ferrand
- J. S. Pedersen
- Jennifer K Dowling
- Julia Como
- K. D. Elgass
- Kimberley D’Costa
- L. Le
- L. S. Tran
- Le Ying
- Maria Kaparakis-Liaskos
- Nina Colon
- Priscilla Johanesen
- Richard L. Ferrero
- Sarah J. Creed
- Seth L Masters
- Thomas Alexander Kufer
- U. Nachbur
Organizations
- National Health and Medical Research Council
- Public Health Agency of Canada
- Victoria State Government