Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection

Zhe Zhao, Huimeng Wang, Mai Shi, Tianyuan Zhu, Troi Pediongco, Xin Yi Lim, Bronwyn S. Meehan, Adam G. Nelson, David P. Fairlie, Jeffrey Y. W. Mak, Sidonia B. G. Eckle, Marcela Moreira, Carolin Tumpach, Michael Bramhall, Cameron G. Williams, Hyun Jae Lee, Ashraful Haque, Maximilien Evrard, Jamie Rossjohn, James McCluskey (), Alexandra J. Corbett () and Zhenjun Chen ()
Additional contact information
Zhe Zhao: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Huimeng Wang: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Mai Shi: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Tianyuan Zhu: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Troi Pediongco: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Xin Yi Lim: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Bronwyn S. Meehan: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Adam G. Nelson: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
David P. Fairlie: Institute for Molecular Bioscience, The University of Queensland
Jeffrey Y. W. Mak: Institute for Molecular Bioscience, The University of Queensland
Sidonia B. G. Eckle: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Marcela Moreira: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Carolin Tumpach: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Michael Bramhall: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Cameron G. Williams: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Hyun Jae Lee: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Ashraful Haque: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Maximilien Evrard: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Jamie Rossjohn: Biomedicine Discovery Institute, Monash University
James McCluskey: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Alexandra J. Corbett: Peter Doherty Institute for Infection and Immunity, The University of Melbourne
Zhenjun Chen: Peter Doherty Institute for Infection and Immunity, The University of Melbourne

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Mucosal-associated Invariant T (MAIT) cells are recognized for their antibacterial functions. The protective capacity of MAIT cells has been demonstrated in murine models of local infection, including in the lungs. Here we show that during systemic infection of mice with Francisella tularensis live vaccine strain results in evident MAIT cell expansion in the liver, lungs, kidney and spleen and peripheral blood. The responding MAIT cells manifest a polarised Th1-like MAIT-1 phenotype, including transcription factor and cytokine profile, and confer a critical role in controlling bacterial load. Post resolution of the primary infection, the expanded MAIT cells form stable memory-like MAIT-1 cell populations, suggesting a basis for vaccination. Indeed, a systemic vaccination with synthetic antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil in combination with CpG adjuvant similarly boosts MAIT cells, and results in enhanced protection against both systemic and local infections with different bacteria. Our study highlights the potential utility of targeting MAIT cells to combat a range of bacterial pathogens.

Date: 2021
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DOI: 10.1038/s41467-021-24570-2

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