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Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic helicobacter pyloriInfection

D'Souza, Criselle, Pediongco, Troi, Wang, Huimeng, Scheerlinck, Jean-Pierre Y., Kostenko, Lyudmila, Esterbauer, Robyn, Stent, Andrew W., Eckle, Sidonia B. G., Meehan, Bronwyn S., Strugnell, Richard A., Cao, Hanwei, Liu, Ligong, Mak, Jeffrey Y. W., Lovrecz, George, Lu, Louis, Fairlie, David P., Rossjohn, Jamie, McCluskey, James, Every, Alison L., Chen, Zhenjun and Corbett, Alexandra J. 2018. Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic helicobacter pyloriInfection. The Journal of Immunology 200 (5) , pp. 1901-1916. 10.4049/jimmunol.1701512
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Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. We observed MAIT cells in proximity to Helicobacter pylori bacteria in human gastric tissue, and so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic gastritis in a mouse H. pylori SS1 infection model. Following infection, MAIT cells accumulated to high numbers in the gastric mucosa of wild-type C57BL/6 mice, and this was even more pronounced in MAIT TCR transgenic mice or in C57BL/6 mice where MAIT cells were preprimed by Ag exposure or prior infection. Gastric MAIT cells possessed an effector memory Tc1/Tc17 phenotype, and were associated with accelerated gastritis characterized by augmented recruitment of neutrophils, macrophages, dendritic cells, eosinophils, and non-MAIT T cells and by marked gastric atrophy. Similarly treated MR1−/− mice, which lack MAIT cells, showed significantly less gastric pathology. Thus, we demonstrate the pathogenic potential of MAIT cells in Helicobacter-associated immunopathology, with implications for other chronic bacterial infections.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of First Compliant Deposit: 17 August 2018
Date of Acceptance: 29 December 2017
Last Modified: 10 Mar 2020 19:35

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