| First Author | Nagata M | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 1 | PubMed ID | 32991669 |
| Mgi Jnum | J:307311 | Mgi Id | MGI:6509788 |
| Doi | 10.1084/jem.20200815 | Citation | Nagata M, et al. (2021) Helicobacter pylori metabolites exacerbate gastritis through C-type lectin receptors. J Exp Med 218(1) |
| abstractText | 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 alpha-glucoside (alphaCAG) and cholesteryl phosphatidyl alpha-glucoside (alphaCPG) 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 alphaCAG and alphaCPG 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. |
