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, Ishida Hideharu Ishida, Shigenori Nagai, Petr Illarionov, Bridget L. Stocker, Mattie S.M. Timmer, Dylan G.M. Smith, Spencer J. Williams, Takeshi Bamba, Tomofumi Miyamoto, Makoto Arita, Ben J. AppelmelkSho Yamasaki*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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-deficient mice, although bacterial burdens remained unchanged. Furthermore, a mutant H. pylori strain lacking aCAG and aCPG exhibited an impaired ability to cause gastritis. Thus H. pylori-specific modification of host cholesterol plays a pathophysiological role that exacerbates gastric inflammation by triggering C-type lectin receptors.

Original languageEnglish
Article numbere20200815
JournalJournal of Experimental Medicine
Volume218
Issue number1
DOIs
Publication statusPublished - 4 Jan 2021

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