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. 1997 Jul;65(7):2693–2699. doi: 10.1128/iai.65.7.2693-2699.1997

Effect of immunoglobulin G isotype on the infectivity of Chlamydia trachomatis in a mouse model of intravaginal infection.

E M Peterson 1, X Cheng 1, V L Motin 1, L M de la Maza 1
PMCID: PMC175380  PMID: 9199438

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.

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Selected References

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  1. Barclay A. N., Mason D. W. Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli. J Exp Med. 1982 Dec 1;156(6):1665–1676. doi: 10.1084/jem.156.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blumberg R. S., Koss T., Story C. M., Barisani D., Polischuk J., Lipin A., Pablo L., Green R., Simister N. E. A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes. J Clin Invest. 1995 May;95(5):2397–2402. doi: 10.1172/JCI117934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brandt W. E., McCown J. M., Top F. H., Jr, Bancroft W. H., Russell P. K. Effect of passage history on dengue-2 virus replication in subpopulations of human leukocytes. Infect Immun. 1979 Nov;26(2):534–541. doi: 10.1128/iai.26.2.534-541.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Byrne G. I., Stephens R. S., Ada G., Caldwell H. D., Su H., Morrison R. P., Van der Pol B., Bavoil P., Bobo L., Everson S. Workshop on in vitro neutralization of Chlamydia trachomatis: summary of proceedings. J Infect Dis. 1993 Aug;168(2):415–420. doi: 10.1093/infdis/168.2.415. [DOI] [PubMed] [Google Scholar]
  5. Bécherel P. A., Mossalayi M. D., Ouaaz F., Le Goff L., Dugas B., Paul-Eugène N., Frances C., Chosidow O., Kilchherr E., Guillosson J. J. Involvement of cyclic AMP and nitric oxide in immunoglobulin E-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes. J Clin Invest. 1994 May;93(5):2275–2279. doi: 10.1172/JCI117227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng X., Pal S., de la Maza L. M., Peterson E. M. Characterization of the humoral response induced by a peptide corresponding to variable domain IV of the major outer membrane protein of Chlamydia trachomatis serovar E. Infect Immun. 1992 Aug;60(8):3428–3432. doi: 10.1128/iai.60.8.3428-3432.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cotter T. W., Meng Q., Shen Z. L., Zhang Y. X., Su H., Caldwell H. D. Protective efficacy of major outer membrane protein-specific immunoglobulin A (IgA) and IgG monoclonal antibodies in a murine model of Chlamydia trachomatis genital tract infection. Infect Immun. 1995 Dec;63(12):4704–4714. doi: 10.1128/iai.63.12.4704-4714.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Denning G. M. IL-4 and IFN-gamma synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. Role of protein tyrosine kinases. J Immunol. 1996 Jun 15;156(12):4807–4814. [PubMed] [Google Scholar]
  9. Henry-Suchet J., Catalan F., Loffredo V., Sanson M. J., Debache C., Pigeau F., Coppin R. Chlamydia trachomatis associated with chronic inflammation in abdominal specimens from women selected for tuboplasty. Fertil Steril. 1981 Nov;36(5):599–605. doi: 10.1016/s0015-0282(16)45857-7. [DOI] [PubMed] [Google Scholar]
  10. Homsy J., Meyer M., Tateno M., Clarkson S., Levy J. A. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science. 1989 Jun 16;244(4910):1357–1360. doi: 10.1126/science.2786647. [DOI] [PubMed] [Google Scholar]
  11. Knight S. C., Iqball S., Woods C., Stagg A., Ward M. E., Tuffrey M. A peptide of Chlamydia trachomatis shown to be a primary T-cell epitope in vitro induces cell-mediated immunity in vivo. Immunology. 1995 May;85(1):8–15. [PMC free article] [PubMed] [Google Scholar]
  12. Mady B. J., Erbe D. V., Kurane I., Fanger M. W., Ennis F. A. Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors. J Immunol. 1991 Nov 1;147(9):3139–3144. [PubMed] [Google Scholar]
  13. Peterson E. M., Cheng X., Markoff B. A., Fielder T. J., de la Maza L. M. Functional and structural mapping of Chlamydia trachomatis species-specific major outer membrane protein epitopes by use of neutralizing monoclonal antibodies. Infect Immun. 1991 Nov;59(11):4147–4153. doi: 10.1128/iai.59.11.4147-4153.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peterson E. M., Cheng X., Pal S., de la Maza L. M. Effects of antibody isotype and host cell type on in vitro neutralization of Chlamydia trachomatis. Infect Immun. 1993 Feb;61(2):498–503. doi: 10.1128/iai.61.2.498-503.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Peterson E. M., Markoff B. A., Schachter J., de la Maza L. M. The 7.5-kb plasmid present in Chlamydia trachomatis is not essential for the growth of this microorganism. Plasmid. 1990 Mar;23(2):144–148. doi: 10.1016/0147-619x(90)90033-9. [DOI] [PubMed] [Google Scholar]
  16. Peterson E. M., Oda R., Tse P., Gastaldi C., Stone S. C., de la Maza L. M. Comparison of a single-antigen microimmunofluorescence assay and inclusion fluorescent-antibody assay for detecting chlamydial antibodies and correlation of the results with neutralizing ability. J Clin Microbiol. 1989 Feb;27(2):350–352. doi: 10.1128/jcm.27.2.350-352.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Qu Z., Cheng X., de la Maza L. M., Peterson E. M. Characterization of a neutralizing monoclonal antibody directed at variable domain I of the major outer membrane protein of Chlamydia trachomatis C-complex serovars. Infect Immun. 1993 Apr;61(4):1365–1370. doi: 10.1128/iai.61.4.1365-1370.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  19. Schachter J. Overview of Chlamydia trachomatis infection and the requirements for a vaccine. Rev Infect Dis. 1985 Nov-Dec;7(6):713–716. doi: 10.1093/clinids/7.6.713. [DOI] [PubMed] [Google Scholar]
  20. Su H., Caldwell H. D. Immunogenicity of a chimeric peptide corresponding to T helper and B cell epitopes of the Chlamydia trachomatis major outer membrane protein. J Exp Med. 1992 Jan 1;175(1):227–235. doi: 10.1084/jem.175.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Su H., Parnell M., Caldwell H. D. Protective efficacy of a parenterally administered MOMP-derived synthetic oligopeptide vaccine in a murine model of Chlamydia trachomatis genital tract infection: serum neutralizing IgG antibodies do not protect against chlamydial genital tract infection. Vaccine. 1995 Aug;13(11):1023–1032. doi: 10.1016/0264-410x(95)00017-u. [DOI] [PubMed] [Google Scholar]
  22. Su H., Raymond L., Rockey D. D., Fischer E., Hackstadt T., Caldwell H. D. A recombinant Chlamydia trachomatis major outer membrane protein binds to heparan sulfate receptors on epithelial cells. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11143–11148. doi: 10.1073/pnas.93.20.11143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Su H., Spangrude G. J., Caldwell H. D. Expression of Fc gamma RIII on HeLa 229 cells: possible effect on in vitro neutralization of Chlamydia trachomatis. Infect Immun. 1991 Oct;59(10):3811–3814. doi: 10.1128/iai.59.10.3811-3814.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Takeda A., Ennis F. A. FcR-mediated enhancement of HIV-1 infection by antibody. AIDS Res Hum Retroviruses. 1990 Aug;6(8):999–1004. doi: 10.1089/aid.1990.6.999. [DOI] [PubMed] [Google Scholar]
  25. Takeda A., Tuazon C. U., Ennis F. A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science. 1988 Oct 28;242(4878):580–583. doi: 10.1126/science.2972065. [DOI] [PubMed] [Google Scholar]
  26. Tuffrey M., Alexander F., Conlan W., Woods C., Ward M. Heterotypic protection of mice against chlamydial salpingitis and colonization of the lower genital tract with a human serovar F isolate of Chlamydia trachomatis by prior immunization with recombinant serovar L1 major outer-membrane protein. J Gen Microbiol. 1992 Aug;138(Pt 8):1707–1715. doi: 10.1099/00221287-138-8-1707. [DOI] [PubMed] [Google Scholar]
  27. Tuffrey M., Falder P., Taylor-Robinson D. Genital-tract infection and disease in nude and immunologically competent mice after inoculation of a human strain of Chlamydia trachomatis. Br J Exp Pathol. 1982 Oct;63(5):539–546. [PMC free article] [PubMed] [Google Scholar]
  28. Ulstein M., Skeie Jensen T., Matre R. Demonstration of Fc gamma receptors in human endometrium. Acta Obstet Gynecol Scand. 1993 Jan;72(1):4–9. doi: 10.3109/00016349309013340. [DOI] [PubMed] [Google Scholar]
  29. Zhang Y. X., Stewart S., Joseph T., Taylor H. R., Caldwell H. D. Protective monoclonal antibodies recognize epitopes located on the major outer membrane protein of Chlamydia trachomatis. J Immunol. 1987 Jan 15;138(2):575–581. [PubMed] [Google Scholar]

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