PT  - JOURNAL ARTICLE
AU  - L. S. Tran
AU  - L. Ying
AU  - K. D’Costa
AU  - G. Wray-McCann
AU  - G. Kerr
AU  - L. Le
AU  - C. C. Allison
AU  - J. Ferrand
AU  - H. Chaudhry
AU  - J. Emery
AU  - A. De Paoli
AU  - S. Creed
AU  - M. Kaparakis-Liaskos
AU  - J. Como
AU  - J. Dowling
AU  - P. A. Johanesen
AU  - T. A. Kufer
AU  - J. S. Pedersen
AU  - A. Mansell
AU  - D. J. Philpott
AU  - K. Elgass
AU  - H. E. Abud
AU  - U. Nachbur
AU  - B. A. Croker
AU  - S. L. Masters
AU  - R. L. Ferrero
TI  - NOD1 mediates non-canonical inflammasome processing of interleukin-18 in epithelial cells to <em>Helicobacter pylori</em> infection
AID  - 10.1101/587212
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 587212
4099  - http://biorxiv.org/content/early/2019/03/24/587212.short
4100  - http://biorxiv.org/content/early/2019/03/24/587212.full
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.