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

• Published in: Frontiers in immunology Vol. 15; p. 1500696
• Main Authors: Clegg, Jonah, Mnich, Malgorzata E., Carignano, Alberto, Cova, Giovanni, Tavarini, Simona, Sammicheli, Chiara, Clemente, Bruna, Smith, Megan, Siena, Emilio, Bardelli, Monia, Brazzoli, Michela, Bagnoli, Fabio, McLoughlin, Rachel M., Soldaini, Elisabetta
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.02.2025
• Subjects: Adult; Cytokines; Female; Healthy Volunteers; host-pathogen interactions; Humans; Immunology; Male; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Staphylococcal Infections - immunology; Staphylococcal Infections - prevention & control; Staphylococcal Vaccines - immunology; Staphylococcus aureus; Staphylococcus aureus - immunology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th17; TIGIT; Treg; Vaccination; vaccines; host-pathogen interactions; colonization; vaccines; Treg; TIGIT; Th17; Staphylococcus aureus
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1500696

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.