Novel immune activating signaling pathway deciphered in epithelial cells infected by H. pylori [27.06.23]
Inflammation is a complex process involving the activation of so-called inflammasomes. These inflammation-specific protein complexes play an important role in the immune response and activate e.g. the interleukins IL-1β and IL-18. For the latter, the activation mechanism has been largely unclear, especially for epithelial cells. A study just published in Nature Communications and co-authored by Hohenheim Professor Thomas Kufer (Dept. Immunology) addresses this issue and identifies a new signaling pathway in epithelial cells that leads to the activation of the immune mediator IL-18 after infection with Helicobacter pylori. Infection with the bacterium H. pylori is known to induce inflammation of the gastric mucosa and can lead to severe gastritic diseases and even cancer.
Picture Source: The oncogenic mechanism of Helicobacter pylori infection.jpg - Wikimedia Commons
Original Paper
Tran LS, Ying L, D'Costa K, Wray-McCann G, Kerr G, Le L, Allison CC, Ferrand J, Chaudhry H, Emery J, De Paoli A, Colon N, Creed S, Kaparakis-Liaskos M, Como J, Dowling JK, Johanesen PA, Kufer TA, Pedersen JS, Mansell A, Philpott DJ, Elgass KD, Abud HE, Nachbur U, Croker BA, Masters SL, Ferrero RL. (2023) NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice. Nat Commun. 2023 Jun 26;14(1):3804. doi: 10.1038/s41467-023-39487-1.
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.
More on the cooperation with Prof. Richard Ferrero
There is a long-standing collaboration of Thomas Kufer with the group of Richard Ferrero. Currently, the cooperation is supported by the German Academic Exchange service in the frame of 'Project Related Exchange of Persons from and to Australia' (Grant No. 57654618) on the topic "Unravelling the reulatory functions of NLRC5 in anti-cancer immunity" from 01/2023 to 12/2024.Prof. Ferrero was part of the SchlossGEISTer seminar series in 2018 and lectured on "Defining new roles for NLR proteins in bacterial infection".
Link to the Hohenheim Co-Author
 | Prof. Dr. Thomas A. KuferDepartment of ImmunologyHead of Department Phone: +49 711 459 24850 | Mail |
