NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection [post]

Richard Ferrero, Le Son Tran, Le Ying, Kimberley D'Costa, Georgie Wray-McCann, Genevieve Kerr, Lena Le, Cody Allison, Jonathan Ferrand, Hassan Chaudhry, Jack Emery, Amanda De Paoli (+14 others)
2020 unpublished
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 well 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 epithelial cells to the mucosal pathogens, Helicobacter
more » ... ogens, Helicobacter pylori and Pseudomonas aeruginosa. We show that IL-18 is important in protecting against pre-neoplastic changes induced by gastric H. pylori infection in vivo. NOD1 mediates IL-18 processing via homotypic CARD-CARD interactions with caspase-1, and independently of canonical inflammasome proteins (NLRP3, ASC). These findings reveal an unanticipated role for NOD1 in the formation of bioactive IL-18, thereby underlining the differences in inflammasome functions between haematopoietic and non-haematopoietic cells.
doi:10.21203/rs.3.rs-49701/v1 fatcat:qgnxcna4rjfrfiblnekz7nfdmu