Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1500696

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

Provisionally accepted
Jonah Clegg Jonah Clegg 1,2Malgorzata Ewa Mnich Malgorzata Ewa Mnich 2,3Alberto Carignano Alberto Carignano 2Giovanni Cova Giovanni Cova 2Simona Tavarini Simona Tavarini 2Chiara Sammicheli Chiara Sammicheli 2Bruna Clemente Bruna Clemente 2Megan Smith Megan Smith 2Emilio Siena Emilio Siena 2Monia Bardelli Monia Bardelli 2Michela Brazzoli Michela Brazzoli 2Fabio Bagnoli Fabio Bagnoli 2Rachel Mary Mcloughlin Rachel Mary Mcloughlin 1Elisabetta Soldaini Elisabetta Soldaini 2*
  • 1 Trinity Biomedical Sciences Institute, Faculty of Engineering, Mathematics and Science, Trinity College Dublin, Dublin, Ireland
  • 2 GlaxoSmithKline (Italy), Siena, Tuscany, Italy
  • 3 Innate Immunity Unit, Institut Pasteur, Paris, France

The final, formatted version of the article will be published soon.

    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-1 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.

    Keywords: Staphylococcus aureus, Th17, Treg, TIGIT, Host-Pathogen Interactions, Vaccines, colonization

    Received: 23 Sep 2024; Accepted: 12 Nov 2024.

    Copyright: © 2024 Clegg, Mnich, Carignano, Cova, Tavarini, Sammicheli, Clemente, Smith, Siena, Bardelli, Brazzoli, Bagnoli, Mcloughlin and Soldaini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Elisabetta Soldaini, GlaxoSmithKline (Italy), Siena, 53100, Tuscany, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.