1. Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses.
- Author
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Purohit SK, Stern L, Corbett AJ, Mak JYW, Fairlie DP, Slobedman B, and Abendroth A
- Subjects
- Humans, Lymphocyte Activation immunology, Cytokines metabolism, Cytokines immunology, Riboflavin immunology, Varicella Zoster Virus Infection immunology, Varicella Zoster Virus Infection virology, Immune Evasion immunology, Herpes Zoster immunology, Herpes Zoster virology, Mucosal-Associated Invariant T Cells immunology, Herpesvirus 3, Human immunology
- Abstract
Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses., Competing Interests: J.Y.W.M., A.J.C., and D.P.F. are inventors on patents describing MAIT cell antigens and tetramers. The authors declare no other potential conflict of interest., (Copyright: © 2024 Purohit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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