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 S M Timmer, Dylan G M Smith, Spencer J Williams, Takeshi Bamba, Tomofumi Miyamoto, Makoto Arita, Ben J Appelmelk, Sho Yamasaki
The Journal of experimental medicine 2021 Jan 04Helicobacter 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-deficient mice, although bacterial burdens remained unchanged. Furthermore, a mutant H. pylori strain lacking αCAG and αCPG 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. © 2020 Nagata et al.
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 S M Timmer, Dylan G M Smith, Spencer J Williams, Takeshi Bamba, Tomofumi Miyamoto, Makoto Arita, Ben J Appelmelk, Sho Yamasaki. Helicobacter pylori metabolites exacerbate gastritis through C-type lectin receptors. The Journal of experimental medicine. 2021 Jan 04;218(1)
PMID: 32991669
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