IL-17A-producing gammadeltaT cells promote CTL responses against Listeria monocytogenes infection by enhancing dendritic cell cross-presentation.
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.
National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, China.
Sheng
S
Xu
Yanmei
Y
Han
Xiongfei
X
Xu
Yan
Y
Bao
Minggang
M
Zhang
Xuetao
X
Cao
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D045142:Cross-Priming / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta