title: Involvement of IL-17A-producing TCR γδ T cells in late protective immunity against pulmonaryMycobacterium tuberculosisinfection.
abstract: Interleukin (IL)-17A is a cytokine originally reported to induce neutrophil-mediated inflammation and anti-microbial activity. The CD4+T cells, which produce IL-17A, have been well characterized as Th17 cells. On the other hand, IL-17A-producing TCR γδ+T cells have been reported to participate in the immune response at an early stage of infection withListeria monocytogenesandMycobacterium bovisin mice. However, the involvement of IL-17A in protective immunity was not clearly demonstrated in the chronic stage ofM. tuberculosis-infected mice.
  
  
  
  We analyzed role of IL-17A in host defense against chronically infectedM. tuberculosisusing IL-17A KO mice.
  
  
  
  We found that TCR γδ+T cells are a primary source of IL-17A, but that mycobacterial antigen-specific Th17 cells were hardly detected even at the chronic stage ofM. tuberculosisinfection. IL-17A-deficient mice showed a decreased survival rate, and increased bacterial burden in the lungs after the infection when compared to the wild-type mice. Furthermore, a histological analysis showed an impaired granuloma formation in the infected lungs of IL-17A-deficient mice, which was considered to be due to a decrease of IFN-γ and TNF at the chronic stage.
  
  
  
  Our data suggest that the IL-17A-producing TCR γδ+T cells, rather than the Th17 cells, in the infected lungs are an indispensable source of protective immunity againstM. tuberculosisinfection.
authors.affiliation: Molecular Microbiology GroupDepartment of Infectious DiseasesTropical Biosphere Research CenterUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan; Department of Host DefenseGraduate School of MedicineUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Molecular Microbiology Group Department of Infectious Diseases Tropical Biosphere Research Center University of the Ryukyus 1 Senbaru Nishihara Okinawa 903-0213 Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamoto-Yoshida
authors.affiliation: Molecular Microbiology Group Department of Infectious Diseases Tropical Biosphere Research Center University of the Ryukyus 1 Senbaru Nishihara Okinawa 903-0213 Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Yahagi
authors.affiliation: Molecular Microbiology GroupDepartment of Infectious DiseasesTropical Biosphere Research CenterUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan; Department of Host DefenseGraduate School of MedicineUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Touyama
authors.affiliation: Laboratory of Systems Biology Center for Experimental Medicine and Systems Biology Institute of Medical Science University of Tokyo 4-6-1 Shiroganedai Minato-ku Tokyo 108-8639 Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Division of Experimental Animal Immunology Center for Animal Disease Models Research Institute for Biomedical Sciences Tokyo University of Science Chiba 278-0022 Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Molecular Microbiology GroupDepartment of Infectious DiseasesTropical Biosphere Research CenterUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan; Department of Host DefenseGraduate School of MedicineUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: IL‐17A; infectious diseases; lung inflammation; γδ T cells