Mark C. Marchitto , Carly A. Dillen , Haiyun Liu , Robert J. Miller , Nathan K. Archer , Roger V. Ortines , Martin P. Alphonse , Alina I. Marusina , Alexander A. Merleev , Yu Wang , Bret L. Pinsker , Angel S. Byrd , Isabelle D. Brown , Advaitaa Ravipati , Emily Zhang , Shuting S. Cai , Nathachit Limjunyawong , Xinzhong Dong , Michael R. Yeaman , Scott I. Simon , Wei Shen , Scott K. Durum , Rebecca L. O’Brien , Emanual Maverakis , Lloyd S. Miller
May 14 2019
T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6 + T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6 +Vδ4 + T cells in immunity against S. aureus skin infections.