Mucosal-associated invariant T cells augment immunopathology in chronic <em>Helicobacter pylori</em> infection — ASN Events
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  3. Mucosal-associated invariant T cells augment immunopathology in chronic Helicobacter pylori infection

Mucosal-associated invariant T cells augment immunopathology in chronic Helicobacter pylori infection (#202)

Criselle D'Souza 1 2 , Troi Pediongco 1 , Huimeng Wang 1 , Jean-Pierre Y Scheerlinck 2 , Lyudmila Kostenko 1 , Robyn Esterbauer 1 , Andrew Stent 2 , Sidonia BG Eckle 1 , Bronwyn S Meehan 1 , Richard A Strugnell 1 , Hanwei Cao 1 , Ligong Liu 3 4 , Jeffrey YM Mak 3 4 , George Lovrecz 5 , Louis Lu 5 , David P Fairlie 3 4 , Jamie Rossjohn 6 7 8 , James McCluskey 1 , Alison L Every 2 , Zhenjun Chen 1 , Alexandra J Corbett 1
  1. Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIc, Australia
  2. Centre for Animal Biotechnology, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Vic, Australia
  3. Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld, Australia
  4. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, Qld, Australia
  5. BioMedical Manufacturing, CSIRO, Melbourne, Vic, Australia
  6. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Vic, Australia
  7. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
  8. ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Vic, Australia

Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines (IL-17, IFNγ, TNF), and cytotoxic granzymes in response to by-products of microbial riboflavin (vitamin B2) synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. MAIT cells could be detected in human gastric tissue using MR1-tetramers. By immunofluorescent staining we observed MAIT cells in proximity to Helicobacter pylori bacilli in gastric tissue from three individuals. In order to determine whether MAIT cells contribute to chronic inflammation and gastritis following Helicobacter infection, we examined the MAIT cell response in a mouse H. pylori SS1 infection model. Following infection, MAIT cells accumulated to high numbers in the gastric mucosa of both MAIT TCR transgenic mice and wild-type C57BL/6 mice with pre-boosted MAIT cells, as well as a proportion of wild-type mice that had no pre-boosting. Gastric MAIT cells possessed an effector memory Tc1/Tc17 phenotype, and were associated with accelerated gastritis characterised by augmented recruitment of neutrophils, macrophages, dendritic cells, eosinophils and non-MAIT T cells. These changes were accompanied by marked gastric atrophy. Interestingly, one long-term infected MAIT TCR transgenic mouse developed gastric lymphoma. Thus, we demonstrate a pathogenic role for MAIT cells in Helicobacter-associated inflammation, revealing a broader potential role for MAIT cell-driven immunopathology in chronic bacterial infection.