Journal article

Helicobacter pylori metabolites exacerbate gastritis through C-type lectin receptors

Masahiro Nagata, Kenji Toyonaga, Eri Ishikawa, Shojiro Haji, Nobuyuki Okahashi, Masatomo Takahashi, Yoshihiro Izumi, Akihiro Imamura, Koichi Takato, Hideharu Ishida, Shigenori Nagai, Petr Illarionov, Bridget L Stocker, Mattie SM Timmer, Dylan GM Smith, Spencer J Williams, Takeshi Bamba, Tomofumi Miyamoto, Makoto Arita, Ben J Appelmelk Show all

Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2021

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 α-glucoside (αCAG) and cholesteryl phosphatidyl α-glucoside (αCPG) 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..

View full abstract

University of Melbourne Researchers

Grants

Awarded by Japan Agency forMedical Research and Development


Awarded by Japan Society for the Promotion of Science KAKENHI


Awarded by Australian Research Council


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.