bims-maitce 2024-12-08 papers

Issue of 2024–12–08
two papers selected by
Andy E. Hogan, Maynooth University

Sci Immunol. 2024 Dec 06. 9(102): eadp9841

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

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

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.

DOI: https://doi.org/10.1126/sciimmunol.adp9841

Pathog Immun. 2024 ;10(1): 19-46

Inflammation and Microbial Translocation Correlate with Reduced MAIT Cells in People with HIV.

Angela Ryu, Brian M Clagett, Michael L Freeman.

Background: Optimal control of microbial infections requires mucosal-associated invariant T (MAIT) cells. People living with HIV (PWH) on antiretroviral therapy (ART) can be divided into 2 groups: immune responders (IR) who recover or retain CD4 T cell numbers, and immune non-responders (INR) who do not. Compared to IR, INR have fewer MAIT cells and increased systemic inflammation and microbial translocation, but how these factors affect MAIT cells is unknown.
Methods: MAIT cells from IR, INR, and from controls without HIV were enumerated and characterized by flow cytometry. To determine the links among MAIT cells, inflammation, and microbial translocation, the correlations of MAIT cell numbers to previously published soluble inflammatory markers and plasma microbial genetic sequences were assessed by Spearman analysis. In vitro assays were used to support our findings.
Results: MAIT cell numbers were significantly negatively correlated with levels of IL-6 and IP-10 (markers of inflammation); CD14, LPS, and FABP2 (markers of microbial translocation); and with abundance of Serratia and other Proteobacteria genetic sequences in plasma. In a separate analysis of PWH on ART receiving the IL-6 receptor antagonist tocilizumab (TCZ), we found that blocking IL-6 signaling with TCZ increased IL-7 receptor expression on MAIT cells and reduced plasma IL-7 levels, consistent with improved uptake of IL-7 in vivo.
Conclusions: Our findings suggest inflammation and microbial translocation in PWH on ART lead to a loss of MAIT cells via impaired IL-7 responsiveness, resulting in further increased microbial translocation and inflammation.

Keywords: HIV; IL-6; Inflammation; MAIT cells; Microbial translocation; Tocilizumab

DOI: https://doi.org/10.20411/pai.v10i1.746