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The role of microbial viability in regulating mucosal associated invariant T (MAIT) cell activation

Year:
2019
Duration:
42 months
Approved budget:
$1,191,634.70
Researchers:
Associate Professor James Ussher
Health issue:
Infectious disease
Proposal type:
Project
Lay summary
Mucosal surfaces are a critical interface with the external environment. The mucosal immune system must be tightly regulated to fight infection while avoiding disease-causing inflammation. Mucosal associated invariant T (MAIT) cells are pro-inflammatory, antibacterial T cells that are abundant at mucosal surfaces. While MAIT cells are primarily activated by a bacterial metabolite, we have recently found that other bacterial components also modulate their activation, and that this is dependent upon phagocytosis of intact bacteria. This suggests that the sensing of microbial viability by antigen presenting cells may be important in modulating their ability to activate MAIT cells. In this study, we will determine the importance of sensing microbial viability for MAIT cell activation, how viability is sensed by antigen presenting cells, and how viability is signalled to MAIT cells. This will enhance our understanding of MAIT cell function and inform the future development of MAIT cell-directed therapies.