RT Journal Article SR Electronic T1 NOD1 mediates non-canonical inflammasome processing of interleukin-18 in epithelial cells to Helicobacter pylori infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 587212 DO 10.1101/587212 A1 L. S. Tran A1 L. Ying A1 K. D’Costa A1 G. Wray-McCann A1 G. Kerr A1 L. Le A1 C. C. Allison A1 J. Ferrand A1 H. Chaudhry A1 J. Emery A1 A. De Paoli A1 S. Creed A1 M. Kaparakis-Liaskos A1 J. Como A1 J. Dowling A1 P. A. Johanesen A1 T. A. Kufer A1 J. S. Pedersen A1 A. Mansell A1 D. J. Philpott A1 K. Elgass A1 H. E. Abud A1 U. Nachbur A1 B. A. Croker A1 S. L. Masters A1 R. L. Ferrero YR 2019 UL http://biorxiv.org/content/early/2019/03/24/587212.abstract AB 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 extensively studied, those involved in IL-18 processing, particularly in non-myeloid cells, are still poorly understood. Here, we have identified the cytosolic sensor NOD1 as a key regulator of IL-18 processing in epithelial cells responding to Helicobacter pylori infection. Importantly, NOD1 processing of IL-18 occurs independently of the canonical inflammasome proteins, NLRP3 and ASC. Instead, NOD1 interacts directly with caspase-1 via homotypic binding of caspase-activation recruitment domains. We show that IL-18 is important in maintaining tissue homeostasis and protecting against pre-neoplastic changes due to gastric H. pylori infection. These findings reveal an unanticipated role for NOD1 in a new type of inflammasome that regulates epithelial cell production of bioactive IL-18 with tissue protective functions.