Mammary gamma delta T cells promote IL17A mediated immunity against Staphylococcus aureus induced mastitis in a microbiota dependent manner

Mastitis, generally caused by Staphylococcus aureus, is a complexity and intractability infection which illustrated by limited efficacy of currently available vaccines and antimicrobial treatment. Detailed understanding of immune mechanism is essential for developing novel strategies to prevent S. aureus induced mastitis; however, as far as we know, it is poorly understood. This study sought to explore the mechanisms of local innate immune response in defense against S. aureus induced mastitis, and determine the role of commensal microbiota in this process. Here, we found that intramammary infection with S. aureus increased IL17A production and neutrophil recruitment in mammary glands in the early stage, and paralleled by an increased in MIP2, KC and MPO. Neutrophil recruitment via IL17A mediated signaling was required for host defense against S. aureus induced mastitis as revealed by decreased ability of bacterial clearance and increased pathological damage of mammary gland in IL17A knockout mice. The rapid accumulation and activation of gamma delta T cells in the early stage of infection triggered the IL17A mediated immune response. Moreover, the potent T cell source of IL17A was from a population of clonotypic V gamma 4 gamma delta T cells. Interestingly, the accumulation and influence of gamma delta T17 cells in host defense against S. aureus induced mastitis in a commensal microbiota dependent manner. Overall, this study, focusing on gamma delta T17 cells, clarified innate immune response mechanisms against S. aureus induced mastitis, and provided a specific response to target for future immunotherapies. Meanwhile, a link between commensal microbiota community and host defense to S. aureus mammary gland infection may unveil novel therapeutic strategies to combat these intractable infections.