title: Effect of immunoglobulin G isotype on the infectivity of Chlamydia trachomatis in a mouse model of intravaginal infection.
abstract: It has been previously shown with an in vitro neutralization system that monoclonal antibodies (MAbs) to the major outer membrane protein (MOMP) of Chlamydia trachomatis, depending on the isotype of the MAb and the host cell used, can either neutralize or enhance the infectivity of this organism. MAbs to variable domain 4 (VD 4) of MOMP have been described that neutralize the infectivity of C. trachomatis when tested in a system in which either the host cell does not have detectable Fc gammaRIII receptors or complement is added to block the interaction of the MAb with the receptor. However, if Fc gammaRIII receptors are available, immunoglobulin G2b (IgG2b) MAbs to the VD 4 are able to enhance the infectivity of this pathogen. Two MAbs that recognize the sequence TLNPTIA in VD 4 of the MOMP but differ in isotype, E4 (IgG2b) and E21 (IgG1), were used to test whether in vivo the isotype of the MAb modulates the outcome of a vaginal infection in a murine model. A third MAb, CP33 (IgG2b), that recognizes the chlamydial lipopolysaccharide but does not neutralize infectivity of C. trachomatis, was also tested. Elementary bodies (EBs) of C. trachomatis, serovar E (BOUR), were pretreated with the three MAbs and were used to inoculate the vaginas of C3H/HeJ mice which had been pretreated with progesterone. Subsequently mice were monitored over a 5-week period with vaginal cultures. In the groups that were inoculated with EBs pretreated with MAbs directed to VD 4 of MOMP, there was a significant decrease (P < 0.05) in the number of mice infected. Only 30% of the mice were infected in the MAb E4-treated group, and 10% were infected in the MAb E21 group. This was in contrast to the groups inoculated with EBs pretreated with MAb CP33 and control untreated EBs, which resulted in 100 and 79% of the mice infected, respectively. Therefore, in this setting in which EBs were introduced in vivo coated with MAb, there was no enhancement of infection by IgG2b MAbs; rather, the results paralled the in vitro neutralization results, in which cells lacking Fc gammaRIII receptors were employed. Mice were also given the MAbs, as well as purified IgG as a control, by intraperitoneal injection before and after intravaginal inoculation with C. trachomatis. Despite relatively high levels of MAbs in serum and detectable levels of MAbs in the vagina at the time of infection, there was only modest protection in animals receiving MAb E21, with 60% of the mice infected in contrast to 90% of the mice receiving MAb E4, MAb CP33, and IgG. However, by the second week of infection compared to controls, there was a significant increase (P < 0.05) in the amount of chlamydiae recovered from the vaginas of mice that had received the two IgG2b MAbs, E4 and CP33. In summary, the presence of IgG2b MAbs directed to surface components of C. trachomatis at certain times during the course of infection may play a role in enhancing the infectivity of this pathogen.
authors.affiliation: Department of Pathology, University of California, Irvine, 92697-4800, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Peterson
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.forename: V L
authors.initials: VL
authors.lastname: Motin
authors.forename: L M
authors.initials: LM
authors.lastname: de la Maza
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology / Q000472:pathogenicity*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D018272:Porins; D017452:Receptors, IgG / Q000032:analysis; D014623:Vaginal Diseases / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D018272:Porins; D017452:Receptors, IgG; C071677:omp1 protein, Chlamydia trachomatis