title: Interleukin-17 contributes to generation of Th1 immunity and neutrophil recruitment during Chlamydia muridarum genital tract infection but is not required for macrophage influx or normal resolution of infection.
abstract: Interleukin 17 (IL-17) contributes to development of Th1 immunity and neutrophil influx during Chlamydia muridarum pulmonary infection, but its role during C. muridarum genital tract infection has not been described. We detected similar numbers of Chlamydia-specific Th17 and Th1 cells in iliac nodes of wild-type mice early during genital C. muridarum infection, while Th1 cells predominated later. il17ra(-/-) mice exhibited a reduced chlamydia-specific Th1 response in draining iliac nodes and decreased local IFN-γ production. Neutrophil influx into the genital tract was also decreased. However, il17ra(-/-) mice resolved infection normally, and no difference in pathology was observed compared to the wild type. Macrophage influx and tumor necrosis factor alpha (TNF-α) production were increased in il17ra(-/-) mice, providing a compensatory mechanism to effectively control chlamydial genital tract infection despite a reduced Th1 response. In ifnγ(-/-) mice, a marked increase in cellular infiltrates and chronic pathology was associated with an increased Th17 response. Although neutralization of IL-17 in ifnγ(-/-) mice decreased neutrophil influx, macrophage infiltration remained intact and the bacterial burden was not increased. Collectively, these results indicate that IL-17 contributes to the generation of Th1 immunity and neutrophil recruitment but is not required for macrophage influx or normal resolution of C. muridarum genital infection. These data highlight the redundant immune mechanisms operative at this mucosal site and the importance of examining site-specific responses to mucosal pathogens.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 13 Children's Way, Slot 512-13, Little Rock, AR 72202, USA. scurlockamym@uams.edu
authors.forename: Amy M
authors.initials: AM
authors.lastname: Scurlock
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Frazer
authors.forename: Charles W
authors.initials: CW
authors.lastname: Andrews
authors.forename: Catherine M
authors.initials: CM
authors.lastname: O'Connell
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Foote
authors.forename: Sarabeth L
authors.initials: SL
authors.lastname: Bailey
authors.forename: Kumar
authors.initials: K
authors.lastname: Chandra-Kuntal
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Toni
authors.initials: T
authors.lastname: Darville
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology*; D010057:Oviducts / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17