MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection.

Wang, Huimeng; Souter, Michael N. T.; de Lima Moreira, Marcela; Li, Shihan; Zhou, Yuchen; Nelson, Adam G.; Yu, Jinhan; Meehan, Lucy J.; Meehan, Bronwyn S.; Eckle, Sidonia B. G.; Lee, Hyun Jae; Schröder, Jan; Haque, Ashraful; Mak, Jeffrey Y. W.; Fairlie, David P.; McCluskey, James; Wang, Zhongfang; Chen, Zhenjun; Corbett, Alexandra J.

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)–producing MAIT1 and interleukin-17A (IL-17A)–producing MAIT17 cell subsets in vivo. Whereas T-bet MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt MAIT17 cells could undergo phenotypic and functional conversion into both RORγt T-bet MAIT1/17 and RORγt−T-bet MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A–secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell–targeted vaccines. Editor's summary: During development, mucosal-associated invariant T (MAIT) cells develop into MAIT1 and MAIT17 subsets with poised effector functions that support homeostatic and antimicrobial responses. Using transcription factor reporter and fate-mapping mice, Wang et al. examined the plasticity of MAIT1 and MAIT17 cells during homeostasis and bacterial infection. RORγt T-bet− MAIT17 cells rapidly converted into RORγt−T-bet MAIT1-like cells, whereas canonical MAIT1 cells were largely resistant to phenotypic conversion. MAIT17 cell–derived MAIT1 cells accumulated in a tissue-specific manner and provided protection against systemic F. tularensis infection. Together, these findings demonstrate that specific patterns of MAIT cell plasticity support their functional adaptation and mucosal protection during bacterial infection. —Claire Olingy

TRANSCRIPTION factors; MUCOUS membranes; BACTERIAL diseases; IMMUNE response; TRANSCRIPTOMES

Science Immunology, 2024, Vol 9, Issue 102, p1

2470-9468

Academic Journal

10.1126/sciimmunol.adp9841