Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Establishing mouse infection models with clinically relevant bacterial strains for examining Mucosal-associated invariant T (MAIT) cell immunity (#248)

Tianyuan Zhu 1 , Mai Shi 1 , Huimeng Wang 1 , Zhe Zhao 1 , Xinyi Lim 1 , Bingjie Wang 1 , Bronwyn Meehan 1 , Lars Kjer-Nielsen 1 , Sidonia Eckle 1 , Tim Stinear 1 , Richard Strugnell 1 , Benjamin Howden 1 , James McCluskey 1 , Alexandra Corbett 1 , Zhenjun Chen 1
  1. Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

Bacterial infections are a global threat to human health and are particularly important in immuno-compromised individuals. Extensive research has been conducted to understand anti-bacterial immunity, often using mouse models of bacterial infections. However, clinical bacteria are often not well suited to infect laboratory animals, which makes it difficult to optimize an in vivo infection model.

MAIT cells are an abundant population of innate-like T cells. MAIT cells are activated by recognizing 5-(2-oxo-propylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a small molecule antigen derived from vitamin B2 (riboflavin) biosynthesis, a shared and essential metabolic pathway for many microorganisms. The role of MAIT cells in control of bacterial infection is only beginning to be elucidated. Recent studies suggest they play a pivotal role in the early immune, either by killing infected cells directly or secreting cytokines. This has been demonstrated in mouse infection models of several bacteria, but most of these bacterial strains were not those seen in human patients.

In this study, we infected laboratory strains of mice with three clinically-important bacteria and investigated the MAIT cell response upon infection. The three bacteria, Klebsiella pneumoniae, Staphylococcus aureus and Escherichia coli, are all clinically important pathogens bearing a riboflavin metabolic pathway and the strains used were isolated from hospitalized patients. Using a MAIT cell reporter assay we found that each of these bacteria could produce antigen to activate MAIT cells when cultured in vitro. In the following in vivo study, we infected C57BL/6 mice with a sub-lethal dose of E. coli and observed an accumulation of MAIT cells at the site of infection. Moreover, MAIT cells were educated to specific functional phenotypes upon infection, as reflected by their secretion of cytokines. These results confirmed the possibility of establishing clinically-relevant bacterial infection models in mice. It is hoped that our study will contribute to filling the gap between bench and bedside.