title: Fc receptor regulation of protective immunity against Chlamydia trachomatis.
abstract: The prevailing paradigm for designing potentially efficacious vaccines against the obligate intracellular bacterium, Chlamydia trachomatis, advocates regimens capable of inducing a mucosal antigen-specific T helper type 1 (Th1) response. However, recent reports indicate that rapid and efficient clearance of a secondary infection also requires certain B-cell functions. We investigated the hypothesis that Fc receptor (FcR)-mediated antibody effector mechanisms are important B-cell-related functions involved in controlling a chlamydial genital reinfection. Microbiological analysis of genital chlamydial infection in FcR knockout (FcRKO) mice lacking the activatory FcgammaRI (CD64) and FcRgammaIII (CD16), as well as the inhibitory FcgammaRIIB1 (CD32), revealed a greater intensity of secondary infection (i.e. bacterial shedding) in FcRminus sign/minus sign as compared to FcR+/+ mice; however, the course of the primary infection was indistinguishable in both animals. Pathologically, FcRKO mice suffered greater ascending infection than immunocompetent wild-type (WT) mice after a secondary infection. Immunological evaluation indicated that the presence of specific anti-chlamydial antibodies enhanced chlamydial antigen presentation for induction of a Th1 response by FcR+/+, but not FcRminus sign/minus sign, antigen-presenting cells. In addition, specific anti-chlamydial antibodies augmented both macrophage killing of infected epithelial cells by antibody-dependent cellular cytotoxicity (ADCC) and macrophage inhibition of productive growth of chlamydiae in co-cultures. These results indicate that B cells participate in anti-chlamydial immunity via FcR-mediated effector functions of antibodies, which are operative during reinfections. Such effector functions include ADCC, and possibly enhanced uptake, processing and presentation of chlamydial antigens for rapid induction of a Th1 response, all facilitating the early clearance of an infection. These findings suggest that a future anti-chlamydial vaccine should elicit both humoral and T-cell-mediated immune responses for optimal memory response and vaccine efficacy.
authors.affiliation: Department of Microbiology and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30320, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Moore
authors.forename: Godwin A
authors.initials: GA
authors.lastname: Ananaba
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bolier
authors.forename: Samera
authors.initials: S
authors.lastname: Bowers
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Belay
authors.forename: Francis O
authors.initials: FO
authors.lastname: Eko
authors.forename: Joseph U
authors.initials: JU
authors.lastname: Igietseme
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000276:immunology*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D011961:Receptors, Fc