The persistence of Helicobacter pylori in the human gastric mucosa implies that the immune response fails to clear the infection. We found that H. pylori compromises the antigen presentation ability of macrophages, because of the decline of the presenting molecules HLA-II. Here, we reveal that the main bacterial factor responsible for this effect is ADP-heptose, an intermediate metabolite in the biosynthetic pathway of lipopolysaccharide (LPS) that elicits a pro-inflammatory response in gastric epithelial cells. In macrophages, it upregulates the expression of miR146b which, in turn, would downmodulate CIITA, the master regulator for HLA-II genes. Hence, H. pylori, utilizing ADP-heptose, exploits a specific arm of macrophage response to establish its survival niche in the face of the immune defense elicited in the gastric mucosa.
ADP-heptose enables Helicobacter pylori to exploit macrophages as a survival niche by suppressing antigen-presenting HLA-II expression / Coletta S.; Battaggia G.; Della Bella C.; Furlani M.; Hauke M.; Faass L.; D'Elios M.M.; Josenhans C.; de Bernard M.. - In: FEBS LETTERS. - ISSN 0014-5793. - STAMPA. - 595:(2021), pp. 2160-2168. [10.1002/1873-3468.14156]
ADP-heptose enables Helicobacter pylori to exploit macrophages as a survival niche by suppressing antigen-presenting HLA-II expression
Coletta S.;Della Bella C.;D'Elios M. M.;
2021
Abstract
The persistence of Helicobacter pylori in the human gastric mucosa implies that the immune response fails to clear the infection. We found that H. pylori compromises the antigen presentation ability of macrophages, because of the decline of the presenting molecules HLA-II. Here, we reveal that the main bacterial factor responsible for this effect is ADP-heptose, an intermediate metabolite in the biosynthetic pathway of lipopolysaccharide (LPS) that elicits a pro-inflammatory response in gastric epithelial cells. In macrophages, it upregulates the expression of miR146b which, in turn, would downmodulate CIITA, the master regulator for HLA-II genes. Hence, H. pylori, utilizing ADP-heptose, exploits a specific arm of macrophage response to establish its survival niche in the face of the immune defense elicited in the gastric mucosa.File | Dimensione | Formato | |
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