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

Le résumé fourni par la source

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.

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