title: Suppression of host adaptive immune responses by Neisseria gonorrhoeae: role of interleukin 10 and type 1 regulatory T cells.
abstract: Infection with Neisseria gonorrhoeae triggers an intense inflammatory response characterized by an influx of neutrophils in the genital tract, yet natural gonococcal infection does not induce a state of protective immunity. Our previous studies in a mouse model of N. gonorrhoeae infection demonstrated that transforming growth factor-β (TGF-β) is involved in the suppression of adaptive immunity by this organism, but complete inhibition of TGF-β activity only partially reverses N. gonorrhoeae-mediated suppression of T helper type 1 (Th1) and Th2 responses. In this study, we show that N. gonorrhoeae strongly induced the production of interleukin (IL)-10 and type 1 regulatory T (Tr1) cells. Blockade of IL-10 and Tr1 cell activity enhanced both Th1/Th2-dependent adaptive immune responses and Th17-governed innate responses to N. gonorrhoeae. Treatment of mice with anti-IL-10 antibody during gonococcal challenge led to faster clearance of infection and induced protection against secondary infection, with the generation of circulating and vaginal anti-gonococcal antibodies. Our results suggest that inhibition of IL-10 and Tr1 cells affords a new approach to the treatment of gonorrhea and facilitates the development of specific protective immunity.
authors.affiliation: Department of Microbiology and Immunology and Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, New York, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, University at Buffalo, Buffalo, New York, USA.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology and Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, New York, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Russell
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006069:Gonorrhea / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000382:microbiology
chemical_list: D000911:Antibodies, Monoclonal; D016753:Interleukin-10