Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?

Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?

Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed charact...

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Main Authors: Jonah Clegg, Malgorzata E. Mnich, Alberto Carignano, Giovanni Cova, Simona Tavarini, Chiara Sammicheli, Bruna Clemente, Megan Smith, Emilio Siena, Monia Bardelli, Michela Brazzoli, Fabio Bagnoli, Rachel M. McLoughlin, Elisabetta Soldaini
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
Subjects:
Staphylococcus aureus
Th17
Treg
TIGIT
host-pathogen interactions
vaccines
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500696/full
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Summary:Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed characterization of their phenotypes and how they might in turn impact vaccine efficacy are thus far unknown. Using an activation induced marker assay to sort for S. aureus-specific CD4+ T cells in an effector function-independent manner, single cell transcriptomic analysis was conducted. Remarkably, S. aureus-specific CD4+ T cells consisted not only of a broader spectrum of conventional T cells (Tcon) than previously described but also of regulatory T cells (Treg). As compared to polyclonally-activated CD4+ T cells, S. aureus-specific Tcon were enriched for the expression of the Th17-type cytokine genes IL17A, IL22 and IL26, while higher percentages of S. aureus-specific Treg expressed the T Cell Immunoreceptor with Ig and ITIM domains (TIGIT), a pleiotropic immune checkpoint. Notably, the antagonistic anti-TIGIT mAb Tiragolumab increased IL-1β production in response to S. aureus in vitro. Therefore, these results uncover the presence of S. aureus-specific TIGIT+ Treg in the blood of healthy subjects that could blunt responses to vaccination and indicate TIGIT as a potential targetable biomarker to overcome pre-exposure-induced immunosuppression.
ISSN:1664-3224

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