IL-17A-producing gammadeltaT cells promote CTL responses against Listeria monocytogenes infection by enhancing dendritic cell cross-presentation

J Immunol. 2010 Nov 15;185(10):5879-87. doi: 10.4049/jimmunol.1001763. Epub 2010 Oct 18.

Abstract

Interleukin-17A-producing T cells, especially Th17, have been shown to be involved in inflammatory autoimmune diseases and host defense against extracellular infections. However, whether and how IL-17A or IL-17A-producing cells can help protection against intracellular bacteria remains controversial, especially how it regulates the adaptive immunity besides recruitment of neutrophils in the innate immune system. By infecting IL-17A-deficient mice with Listeria monocytogenes, we show in this study that IL-17A is required for the generation of Ag-specific CD8(+) CTL response against primary infection, but not for the generation of memory CD8(+) T cells against secondary challenge. Interestingly, we identify γδT cells, but not conventional CD4(+) Th17 cells, as the main cells for innate IL-17A production during L. monocytogenes infection. Furthermore, γδT cells are found to promote Ag-specific CD8(+) T cell proliferation by enhancing cross-presentation of dendritic cells through IL-17A. Adoptive transfer of Il17a(+/+) γδT cells, but not Il17a(-/-) γδT cells or Il17a(+/+) CD4(+) T cells, were sufficient to recover dendritic cells cross-presentation and defective CD8(+) T cell response in Il17a(-/-) mice. Our findings indicate an important role of infection-inducible IL-17A-producing γδT cells and their derived IL-17A against intracellular bacterial infection, providing a mechanism of IL-17A for regulation of innate and adaptive immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Separation
  • Cross-Priming / immunology*
  • Cytotoxicity, Immunologic / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / immunology
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology*
  • Listeriosis / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta