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: Terri Moore, Godwin A Ananaba, Jacqueline Bolier, Samera Bowers, Tesfaye Belay, Francis O Eko, Joseph U Igietseme
• Journal: Immunology (Immunology) Vol. 105 Issue 2 Pg. 213-21 (Feb 2002) ISSN: 0019-2805 [Print] England
• PMID: 11872097 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Bacterial
• Receptors, Fc

Topics

• Animals
• Antibodies, Bacterial (immunology)
• Antibody-Dependent Cell Cytotoxicity
• Antigen Presentation (immunology)
• B-Lymphocytes (immunology)
• Cells, Cultured
• Chlamydia Infections (immunology, microbiology)
• Chlamydia trachomatis (immunology)
• Coculture Techniques
• Epithelial Cells (immunology, microbiology)
• Female
• Genital Diseases, Female (immunology)
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Fc (genetics, immunology)
• Th1 Cells (immunology)