Activation of Human Vδ2⁺ γδ T Cells by Staphylococcus aureus Promotes Enhanced Anti-Staphylococcal Adaptive Immunity

Murine studies have shown the potential for γδ T cells to mediate immunity to Staphylococcus aureus in multiple tissue settings by the secretion of diverse cytokines. However, the role played by γδ T cells in human immune responses to S. aureus is almost entirely unknown. In this study, we establish the capacity of human Vδ2⁺ γδ T cells for rapid activation in response to S. aureus In coculture with S. aureus-infected monocyte-derived dendritic cells (DCs), Vδ2⁺ cells derived from peripheral blood rapidly upregulate CD69 and secrete high levels of IFN-γ. DCs mediate this response through direct contact and IL-12 secretion. In turn, IFN-γ released by Vδ2⁺ cells upregulates IL-12 secretion by DCs in a positive feedback loop. Furthermore, coculture with γδ T cells results in heightened expression of the costimulatory molecule CD86 and the lymph node homing molecule CCR7 on S. aureus-infected DCs. In cocultures of CD4⁺ T cells with S. aureus-infected DCs, the addition of γδ T cells results in heightened CD4⁺ T cell activation. Our findings identify γδ T cells as potential key players in the early host response to S. aureus during bloodstream infection, promoting enhanced responses by both innate and adaptive immune cell populations, and support their consideration in the development of host-directed anti-S. aureus treatments.