Helicobacter pylori metabolites exacerbate gastritis through C-type lectin receptors
Open Access
- 29 September 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (1)
- https://doi.org/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 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.Keywords
Funding Information
- Japan Agency for Medical Research and Development (JP19gm0910010, JP19ak0101070, JP19fk0108075)
- Japan Society for the Promotion of Science (JP17H04087, JP15H05897)
- Australian Research Council (DP160100597)
- Takeda Science Foundation
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