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

Zhao, Zhe, Wang, Huimeng, Shi, Mai, Zhu, Tianyuan, Pediongco, Troi, Lim, Xin Yi, Meehan, Bronwyn S., Nelson, Adam G., Fairlie, David P., Mak, Jeffrey Y. W., Eckle, Sidonia B. G., de Lima Moreira, Marcela, Tumpach, Carolin, Bramhall, Michael, Williams, Cameron G., Lee, Hyun Jae, Haque, Ashraful, Evrard, Maximilien, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, McCluskey, James, Corbett, Alexandra J. and Chen, Zhenjun 2021. Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection. Nature Communications 12 , 4355. 10.1038/s41467-021-24570-2

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	2 September 2021
Date of Acceptance:	15 June 2021
Last Modified:	05 May 2023 09:34
URI:	https://orca.cardiff.ac.uk/id/eprint/143821

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