Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
Aug 2024
Historique:
received: 29 01 2024
accepted: 25 06 2024
medline: 8 8 2024
pubmed: 7 8 2024
entrez: 7 8 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 39110717
doi: 10.1371/journal.ppat.1012372
pii: PPATHOGENS-D-24-00216
doi:

Substances chimiques

Cytokines 0
Riboflavin TLM2976OFR

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1012372

Informations de copyright

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.

Déclaration de conflit d'intérêts

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.

Auteurs

Shivam K Purohit (SK)

Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

Lauren Stern (L)

Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

Alexandra J Corbett (AJ)

Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

Jeffrey Y W Mak (JYW)

ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.

David P Fairlie (DP)

ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.

Barry Slobedman (B)

Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

Allison Abendroth (A)

Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

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Classifications MeSH