Journal article

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 YW Mak, Sidonia BG Eckle, Marcela de Lima Moreira, Carolin Tumpach, Michael Bramhall, Cameron G Williams, Hyun Jae Lee, Ashraful Haque, Maximilien Evrard, Jamie Rossjohn, James McCluskey Show all



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 cel..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH)

Awarded by Australian Research Council (ARC)

Awarded by DECRA Fellowship

Awarded by NHMRC

Awarded by ARC

Awarded by Australian ARC

Funding Acknowledgements

This research was supported by the National Health and Medical Research Council of Australia (NHMRC) (1113293, 1120467, 1125493, and 1193745) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) (R01AI148407). A.J.C. is supported by a Future Fellowship (FT160100083) from the Australian Research Council (ARC) and a Dame Kate Campbell Research Fellowship from the University of Melbourne. S.B.G.E. was supported by a DECRA Fellowship (DE170100407, ARC) and an NHMRC Investigator Fellowship (1196881). D.P.F. andJ.R. acknowledge support from the ARC (CE140100011). D.P.F. was supported by an NHMRC Senior Principal Research Fellowship (1117017). J.R. is an Australian ARC Laureate Fellow (FL160100049). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, NHMRC, or ARC. This work was kindly supported by the Harold and Cora Brennen Benevolent Trust through the purchase of the 10X Chromium Controller. We thank Professor Dale Godfrey for critical review of the work; Tina Luke and the staff at the Doherty Institute node of the Melbourne Cytometry Platform for facility access and technical assistance; and Dr Wei-Jen Chua and Dr Ted Hansen for their kind provision of the 26.5 and 8F2.F9 mAb. F. tularensis LVS and L. longbeachae NSW150 were kindly provided by Dr. Thomas J. Inzana (Virginia Tech, USA) and Dr. Hayley Newton (University of Melbourne, Doherty Institute, Australia), respectively.