Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in γδ but not αβ T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vγ5+ γδ T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R–deficient mice had a phenotype similar to that of γδ T cell–deficient mice. Importantly, γδ T cell–deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17–producing epidermal γδ T cells in innate immunity against S. aureus cutaneous infection.
John S. Cho, Eric M. Pietras, Nairy C. Garcia, Romela Irene Ramos, David M. Farzam, Holly R. Monroe, Julie E. Magorien, Andrew Blauvelt, Jay K. Kolls, Ambrose L. Cheung, Genhong Cheng, Robert L. Modlin, Lloyd S. Miller
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