Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
PLoS Pathog. 2024 Aug 7;20(8):e1012372. doi: 10.1371/journal.ppat.1012372. eCollection 2024 Aug.
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.
黏膜相关不变 T（MAIT）细胞是一种非常规 T 细胞，分别通过 TCR 依赖和非依赖途径对核黄素生物合成和细胞因子作出反应。MAIT 细胞的激活在针对多种病原体的免疫保护中发挥作用，然而，直接感染或暴露于传染性病原体后 MAIT 细胞的功能能力仍未得到明确界定。我们研究了水痘带状疱疹病毒（VZV）对血液衍生的 MAIT 细胞的影响，并报告了 VZV 感染（抗原+）和 VZV 暴露（抗原-）MAIT 细胞在 TCR 依赖和非依赖刺激下对激活、细胞因子产生和转录因子表达的改变。此外，我们揭示了 VZV 暴露（抗原-）MAIT 细胞的抑制不是由邻近的 VZV 感染（抗原+）MAIT 细胞的可溶性因子介导的。最后，我们证明 VZV 损害了 MAIT 细胞对合成核黄素的细菌的细胞溶解能力。总之，我们报告了一种病毒介导的免疫逃避策略，使 MAIT 细胞的反应失去作用。
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