2. Academic Validation
  3. MAIT cell responses to S. aureus and sensitivity to HlgAB are modulated by activation and tissue-dependent virulence effects

MAIT cell responses to S. aureus and sensitivity to HlgAB are modulated by activation and tissue-dependent virulence effects

  • bioRxiv. 2026 Mar 19:2026.03.17.712383. doi: 10.64898/2026.03.17.712383.
Elisa J M Raineri 1,  Caroline Boulouis 1,  Elli Mouchtaridi 1,  Vera Nilsén 1 2 3,  Curtis Cai 1,  Tobias Kammann 1,  Juliette Tabusse 1,  Takuya Sekine 1,  Nicole Wild 4,  Christian Constantz 1,  Eoghann White 1,  Thomas R Müller 1,  Anne Marchalot 1,  Sabrina Ferreira 1,  Jyotsana Kaushal 1,  Akhirunnesa Mily 1,  Miriam Franklin 1,  Elena Bonaiti 4,  Mary-Lyn Eichhorn 4,  John Bassett 1,  Chris Stamper 1,  Jeffrey Y W Mak 5,  David P Fairlie 5,  Chris Tibbitt 1,  Anna Norrby-Teglund 1,  Nicole Marquardt 4,  Jenny Mjösberg 1,  Carl Jorns 2 3,  Jenny Driving 6,  Edwin Leeansyah 1,  Marcus Buggert 1,  Johan K Sandberg 1
Affiliations

Affiliations

  • 1 Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 2 ME Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • 3 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
  • 4 Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • 5 Centre for Chemistry and Drug Discovery, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • 6 Capio Öron Näsa Hals Globen/Odenplan, Stockholm, Sweden.
PMID: 41890076 DOI: 10.64898/2026.03.17.712383
Abstract

Mucosa-associated invariant T (MAIT) cells are unconventional T cells with innate-like rapid antimicrobial effector functions and serve as resident sentinels at mucosal and non-mucosal barriers. However, their role in immune defense against Staphylococcus aureus and the impact of Bacterial immune evasion mechanisms are incompletely understood. Here, we have investigated MAIT cell responses to S. aureus and the impact of its broadly expressed leukocidin toxin HlgAB on MAIT cell responses in different human tissue sites. MAIT cells respond to S. aureus with a complex polyfunctional profile spanning pro-inflammatory IL-17, TNF, and IFNγ, anti-inflammatory IL-10, plus granzymes A, B, and K, perforin, and granulysin. The quality of responses was influenced by microbial dose and time of exposure and was dependent on both MR1-presented antigen and cytokine co-activation. CD56+ MAIT cells displayed stronger effector responses and higher HlgAB sensitivity compared to CD56- cells. MAIT cells were partially resistant to HlgAB-toxicity compared to monocytes; blood-derived MAIT cells remained susceptible, whereas tonsillar MAIT cells showed minimal sensitivity. Notably, activation reduced the MAIT cell susceptibility to HlgAB, and such activation also afforded indirect protection to monocytes in co-cultures. The reduced susceptibility of tonsillar MAIT cells correlated with lower CCR2 and CXCR1 expression, a pattern shared with barrier tissues such as the lung and intestines. In conclusion, these findings indicate that MAIT cells exhibit tissue- and context-dependent responses to S. aureus and sensitivity to HlgAB-mediated immune evasion.

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