RRC ID 65149
Author Tran LS, Tran D, De Paoli A, D'Costa K, Creed SJ, Ng GZ, Le L, Sutton P, Silke J, Nachbur U, Ferrero RL.
Title NOD1 is required for Helicobacter pylori induction of IL-33 responses in gastric epithelial cells.
Journal Cell Microbiol
Abstract Helicobacter pylori (H. pylori) causes chronic inflammation which is a key precursor to gastric carcinogenesis. It has been suggested that H. pylori may limit this immunopathology by inducing the production of interleukin 33 (IL-33) in gastric epithelial cells, thus promoting T helper 2 immune responses. The molecular mechanism underlying IL-33 production in response to H. pylori infection, however, remains unknown. In this study, we demonstrate that H. pylori activates signalling via the pathogen recognition molecule Nucleotide-Binding Oligomerisation Domain-Containing Protein 1 (NOD1) and its adaptor protein receptor-interacting serine-threonine Kinase 2, to promote production of both full-length and processed IL-33 in gastric epithelial cells. Furthermore, IL-33 responses were dependent on the actions of the H. pylori Type IV secretion system, required for activation of the NOD1 pathway, as well as on the Type IV secretion system effector protein, CagA. Importantly, Nod1+/+ mice with chronic H. pylori infection exhibited significantly increased gastric IL-33 and splenic IL-13 responses, but decreased IFN-γ responses, when compared with Nod1-/- animals. Collectively, our data identify NOD1 as an important regulator of mucosal IL-33 responses in H. pylori infection. We suggest that NOD1 may play a role in protection against excessive inflammation.
Volume 20(5)
Pages e12826
Published 2018-5-1
DOI 10.1111/cmi.12826
PMID 29392836
MeSH Animals Cell Line Epithelial Cells / microbiology Epithelial Cells / pathology Gastric Mucosa / immunology Gastric Mucosa / microbiology Helicobacter Infections / genetics* Helicobacter Infections / immunology Helicobacter Infections / microbiology Helicobacter pylori / genetics Helicobacter pylori / immunology Helicobacter pylori / pathogenicity* Humans Immunity, Mucosal / genetics Inflammation / genetics Inflammation / immunology Inflammation / microbiology Interferon-gamma / genetics Interleukin-33 / genetics* Mice Nod1 Signaling Adaptor Protein / genetics* Receptors, Interleukin-13 / genetics* Th2 Cells / immunology Th2 Cells / microbiology
IF 3.43
Human and Animal Cells GSM06(RCB1779)