Open AccessNOD1 is required for Helicobacter pylori induction of IL‐33 responses in gastric epithelial cells
Author(s) -
Tran Le Son,
Tran Darren,
De Paoli Amanda,
D'Costa Kimberley,
Creed Sarah J.,
Ng Garrett Z.,
Le Lena,
Sutton Philip,
Silke J.,
Nachbur U.,
Ferrero Richard L.
Publication year - 2018
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12826
Subject(s) - nod1 , caga , biology , helicobacter pylori , secretion , inflammation , immune system , immunology , gastric mucosa , interleukin 10 , effector , innate immune system , stomach , nod2 , endocrinology , gene , biochemistry , genetics , virulence
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.