TY - JOUR
T1 - Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic helicobacter pylori infection
AU - D'Souza, Criselle
AU - Pediongco, Troi
AU - Wang, Huimeng
AU - Scheerlinck, Jean Pierre Y.
AU - Kostenko, Lyudmila
AU - Esterbauer, Robyn
AU - Stent, Andrew W.
AU - Eckle, Sidonia B.G.
AU - Meehan, Bronwyn S.
AU - Strugnell, Richard A.
AU - Cao, Hanwei
AU - Liu, Ligong
AU - Mak, Jeffrey Y.W.
AU - Lovrecz, George
AU - Lu, Louis
AU - Fairlie, David P.
AU - Rossjohn, Jamie
AU - McCluskey, James
AU - Every, Alison L.
AU - Chen, Zhenjun
AU - Corbett, Alexandra J.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044731141&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1701512
DO - 10.4049/jimmunol.1701512
M3 - Article
AN - SCOPUS:85044731141
VL - 200
SP - 1901
EP - 1916
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -