1. Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection.
- Author
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Zhao Z, Wang H, Shi M, Zhu T, Pediongco T, Lim XY, Meehan BS, Nelson AG, Fairlie DP, Mak JYW, Eckle SBG, de Lima Moreira M, Tumpach C, Bramhall M, Williams CG, Lee HJ, Haque A, Evrard M, Rossjohn J, McCluskey J, Corbett AJ, and Chen Z
- Subjects
- Adjuvants, Immunologic, Animals, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I immunology, Liver immunology, Lung immunology, Mice, Mice, Knockout, Minor Histocompatibility Antigens genetics, Minor Histocompatibility Antigens immunology, Mucosal-Associated Invariant T Cells metabolism, Phenotype, RNA-Seq, Ribitol analogs & derivatives, Ribitol immunology, Single-Cell Analysis, Spleen immunology, Th1 Cells immunology, Th1 Cells metabolism, Transcriptome genetics, Uracil analogs & derivatives, Uracil immunology, Vaccines, Attenuated immunology, Cytokines metabolism, Francisella tularensis immunology, Immunity, Innate, Mucosal-Associated Invariant T Cells immunology
- 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., (© 2021. The Author(s).)
- Published
- 2021
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