title: IL-17/Th17 promotes type 1 T cell immunity against pulmonary intracellular bacterial infection through modulating dendritic cell function.
abstract: Although their contribution to host defense against extracellular infections has been well defined, IL-17 and Th17 are generally thought to have limited impact on intracellular infections. In this study, we investigated the role and mechanisms of IL-17/Th17 in host defense against Chlamydia muridarum, an obligate intracellular bacterium, lung infection. Our data showed rapid increase in IL-17 production and expansion of Th17 cells following C. muridarum infection and significant detrimental impact of in vivo IL-17 neutralization by anti-IL-17 mAb on disease course, immune response, and dendritic cell (DC) function. Specifically, IL-17-neutralized mice exhibited significantly greater body weight loss, higher organism growth, and much more severe pathological changes in the lung compared with sham-treated control mice. Immunological analysis showed that IL-17 neutralization significantly reduced Chlamydia-specific Th1 responses, but increased Th2 responses. Interestingly, the DC isolated from IL-17-neutralized mice showed lower CD40 and MHC II expression and IL-12 production, but higher IL-10 production compared with those from sham-treated mice. In two DC-T cell coculture systems, DC isolated from IL-17-neutralized mice induced higher IL-4, but lower IFN-gamma production by Ag-specific T cells than those from sham-treated mice in cell priming and reaction settings. Adoptive transfer of DC isolated from IL-17-neutralized mice, unlike those from sham-treated mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that IL-17/Th17 plays an important role in host defense against intracellular bacterial infection, and suggest that IL-17/Th17 can promote type 1 T cell immunity through modulating DC function.
authors.affiliation: Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Bai
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Antony George
authors.initials: AG
authors.lastname: Joyee
authors.forename: Yijun
authors.initials: Y
authors.lastname: Fan
authors.forename: Shuhe
authors.initials: S
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Jiao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D005260:Female; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*
chemical_list: D020381:Interleukin-17