Clonal Vγ6+Vδ4+ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection

Mark C. Marchitto, Carly A. Dillen, Haiyun Liu, Robert J. Miller, Nathan 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. SimonWei Shen, Scott K. Durum, Rebecca L. O’Brien, Emanual Maverakis, Lloyd S Miller

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10917-10926
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume166
Issue number22
DOIs
StatePublished - May 28 2019

Keywords

  • IL-17
  • Neutrophils
  • Skin
  • Staphylococcus aureus
  • T cells

ASJC Scopus subject areas

  • General

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    Marchitto, M. C., Dillen, C. A., Liu, H., Miller, R. J., Archer, N., Ortines, R. V., Alphonse, M. P., Marusina, A. I., Merleev, A. A., Wang, Y., Pinsker, B. L., Byrd, A. S., Brown, I. D., Ravipati, A., Zhang, E., Cai, S. S., Limjunyawong, N., Dong, X., Yeaman, M. R., ... Miller, L. S. (2019). Clonal Vγ6+Vδ4+ T cells promote IL-17–mediated immunity against Staphylococcus aureus skin infection. Proceedings of the National Academy of Sciences of the United States of America, 166(22), 10917-10926. https://doi.org/10.1073/pnas.1818256116