Journal article
Helicobacter pylori metabolites exacerbate gastritis through C-type lectin receptors
M Nagata, K Toyonaga, E Ishikawa, S Haji, N Okahashi, M Takahashi, Y Izumi, A Imamura, K Takato, undefined Hideharu Ishida, S Nagai, P Illarionov, BL Stocker, MSM Timmer, DGM Smith, SJ Williams, T Bamba, T Miyamoto, M Arita, BJ Appelmelk Show all
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2021
DOI: 10.1084/JEM.20200815
Abstract
Helicobacter pylori causes gastritis, which has been attributed to the development of H. pylori-specific T cells during infection. However, the mechanism underlying innate immune detection leading to the priming of T cells is not fully understood, as H. pylori evades TLR detection. Here, we report that H. pylori metabolites modified from host cholesterol exacerbate gastritis through the interaction with C-type lectin receptors. Cholesteryl acyl a-glucoside (aCAG) and cholesteryl phosphatidyl a-glucoside (aCPG) were identified as noncanonical ligands for Mincle (Clec4e) and DCAR (Clec4b1). During chronic infection, H. pylori-specific T cell responses and gastritis were ameliorated in Mincle-d..
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Awarded by Osaka University
Funding Acknowledgements
We thank S. Iwai, S. Torigoe, Y. Hosono, and J. Maaskant for technical support; H. Mimuro, E. Kuroda, T. Watanabe, and M. Ito for discussion; M. Tanaka, Y. Baba, K. Kaseda, and M. Ikawa for embryonic engineering; D. Motooka and D. Okuzaki for bioinformatics analysis; and the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University, and Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, for technical support. This research was supported by the Japan Agency forMedical Research and Development (JP19gm0910010, JP19ak0101070, and JP19fk0108075), Japan Society for the Promotion of Science KAKENHI (JP17H04087 and JP15H05897), the Australian Research Council (DP160100597), and the Takeda Science Foundation.