Abstract
Despite significant advances in our understanding of the biology and antigenic structure of Chlamydia trachomatis, and the epidemiology and clinical spectrum of chlamydial disease, the magnitude of morbidity from human chlamydial infections remains an important public health concern. Control of chlamydial disease will likely depend on a multidisciplinary approach, including the development of immunoprophylactic or immunotherapeutic strategies. Reasonable progress has been made in understanding specific immune mechanisms that contribute to host immunity in experimental models of chlamydial infection. However, studies of human immunity have not been so successful. This is particularly evident in that studies to address the development and role of mucosal immune responses to urogenital chlamydial infections have not been forthcoming. The following review is a brief summary of our current knowledge of protective immunity to chlamydial urogenital infections of females. It is not meant to be exhaustive, but instead to touch upon aspects of protective immunity that have been described in both human and experimental animal models of chlamydial infection.
Full Text
The Full Text of this article is available as a PDF (760.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alani M. D., Darougar S., Burns D. C., Thin R. N., Dunn H. Isolation of Chlamydia trachomatis from the male urethra. Br J Vener Dis. 1977 Apr;53(2):88–92. doi: 10.1136/sti.53.2.88. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barenfanger J., MacDonald A. B. The role of immunoglobulin in the neutralization of trachoma infectivity. J Immunol. 1974 Nov;113(5):1607–1617. [PubMed] [Google Scholar]
- Batteiger B. E., Rank R. G. Analysis of the humoral immune response to chlamydial genital infection in guinea pigs. Infect Immun. 1987 Aug;55(8):1767–1773. doi: 10.1128/iai.55.8.1767-1773.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beatty P. R., Stephens R. S. CD8+ T lymphocyte-mediated lysis of Chlamydia-infected L cells using an endogenous antigen pathway. J Immunol. 1994 Nov 15;153(10):4588–4595. [PubMed] [Google Scholar]
- Brunham R. C., Kuo C. C., Cles L., Holmes K. K. Correlation of host immune response with quantitative recovery of Chlamydia trachomatis from the human endocervix. Infect Immun. 1983 Mar;39(3):1491–1494. doi: 10.1128/iai.39.3.1491-1494.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunham R. C., Martin D. H., Kuo C. C., Wang S. P., Stevens C. E., Hubbard T., Holmes K. K. Cellular immune response during uncomplicated genital infection with Chlamydia trachomatis in humans. Infect Immun. 1981 Oct;34(1):98–104. doi: 10.1128/iai.34.1.98-104.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunham R. C., Peeling R., Maclean I., McDowell J., Persson K., Osser S. Postabortal Chlamydia trachomatis salpingitis: correlating risk with antigen-specific serological responses and with neutralization. J Infect Dis. 1987 Apr;155(4):749–755. doi: 10.1093/infdis/155.4.749. [DOI] [PubMed] [Google Scholar]
- Byrne G. I., Grubbs B., Dickey T. J., Schachter J., Williams D. M. Interferon in recovery from pneumonia due to Chlamydia trachomatis in the mouse. J Infect Dis. 1987 Dec;156(6):993–996. doi: 10.1093/infdis/156.6.993. [DOI] [PubMed] [Google Scholar]
- Cain T. K., Rank R. G. Local Th1-like responses are induced by intravaginal infection of mice with the mouse pneumonitis biovar of Chlamydia trachomatis. Infect Immun. 1995 May;63(5):1784–1789. doi: 10.1128/iai.63.5.1784-1789.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cevenini R., Rumpianesi F., Donati M., Moroni A., Sambri V., La Placa M. Class specific immunoglobulin response to individual polypeptides of Chlamydia trachomatis, elementary bodies, and reticulate bodies in patients with chlamydial infection. J Clin Pathol. 1986 Dec;39(12):1313–1316. doi: 10.1136/jcp.39.12.1313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cevenini R., Rumpianesi F., Sambri V., La Placa M. Antigenic specificity of serological response in Chlamydia trachomatis urethritis detected by immunoblotting. J Clin Pathol. 1986 Mar;39(3):325–327. doi: 10.1136/jcp.39.3.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cevenini R., Sarov I., Rumpianesi F., Donati M., Melega C., Varotti C., La Placa M. Serum specific IgA antibody to Chlamydia trachomatis in patients with chlamydial infections detected by ELISA and an immunofluorescence test. J Clin Pathol. 1984 Jun;37(6):686–691. doi: 10.1136/jcp.37.6.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Darougar S. The humoral immune response to chlamydial infection in humans. Rev Infect Dis. 1985 Nov-Dec;7(6):726–730. doi: 10.1093/clinids/7.6.726. [DOI] [PubMed] [Google Scholar]
- Grayston J. T., Wang S. P., Yeh L. J., Kuo C. C. Importance of reinfection in the pathogenesis of trachoma. Rev Infect Dis. 1985 Nov-Dec;7(6):717–725. doi: 10.1093/clinids/7.6.717. [DOI] [PubMed] [Google Scholar]
- Grayston J. T., Wang S. New knowledge of chlamydiae and the diseases they cause. J Infect Dis. 1975 Jul;132(1):87–105. doi: 10.1093/infdis/132.1.87. [DOI] [PubMed] [Google Scholar]
- Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
- Hallberg T., Wölner-Hanssen P., Mårdh P. A. Pelvic inflammatory disease in patients infected with Chlamydia trachomatis: in vitro cell mediated immune response to chlamydial antigens. Genitourin Med. 1985 Aug;61(4):247–251. doi: 10.1136/sti.61.4.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanna L., Schmidt L., Sharp M., Stites D. P., Jawetz E. Human cell-mediated immune responses to chlamydial antigens. Infect Immun. 1979 Feb;23(2):412–417. doi: 10.1128/iai.23.2.412-417.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Igietseme J. U., Magee D. M., Williams D. M., Rank R. G. Role for CD8+ T cells in antichlamydial immunity defined by Chlamydia-specific T-lymphocyte clones. Infect Immun. 1994 Nov;62(11):5195–5197. doi: 10.1128/iai.62.11.5195-5197.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Igietseme J. U., Ramsey K. H., Magee D. M., Williams D. M., Kincy T. J., Rank R. G. Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone. Reg Immunol. 1993 Nov-Dec;5(6):317–324. [PubMed] [Google Scholar]
- Jawetz E., Rose L., Hanna L., Thygeson P. Experimental inclusion conjunctivitis in man: measurements of infectivity and resistance. JAMA. 1965 Nov 8;194(6):620–632. [PubMed] [Google Scholar]
- Katz B. P., Batteiger B. E., Jones R. B. Effect of prior sexually transmitted disease on the isolation of Chlamydia trachomatis. Sex Transm Dis. 1987 Jul-Sep;14(3):160–164. doi: 10.1097/00007435-198707000-00008. [DOI] [PubMed] [Google Scholar]
- Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991 Apr 4;350(6317):423–426. doi: 10.1038/350423a0. [DOI] [PubMed] [Google Scholar]
- Koller B. H., Smithies O. Inactivating the beta 2-microglobulin locus in mouse embryonic stem cells by homologous recombination. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8932–8935. doi: 10.1073/pnas.86.22.8932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lammert J. K. Cytotoxic cells induced after Chlamydia psittaci infection in mice. Infect Immun. 1982 Mar;35(3):1011–1017. doi: 10.1128/iai.35.3.1011-1017.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landers D. V., Erlich K., Sung M., Schachter J. Role of L3T4-bearing T-cell populations in experimental murine chlamydial salpingitis. Infect Immun. 1991 Oct;59(10):3774–3777. doi: 10.1128/iai.59.10.3774-3777.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrison R. P., Feilzer K., Tumas D. B. Gene knockout mice establish a primary protective role for major histocompatibility complex class II-restricted responses in Chlamydia trachomatis genital tract infection. Infect Immun. 1995 Dec;63(12):4661–4668. doi: 10.1128/iai.63.12.4661-4668.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray E. S., Charbonnet L. T., MacDonald A. B. Immunity to chlamydial infections of the eye. I. The role of circulatory and secretory antibodies in resistance to reinfection with guinea pig inclusion conjunctivitis. J Immunol. 1973 Jun;110(6):1518–1525. [PubMed] [Google Scholar]
- Murray E. S., Radcliffe F. T. Immunologic studies in guinea pigs with guinea pig inclusion conjunctivitis (GP-IC) Bedsonia. Am J Ophthalmol. 1967 May;63(5 Suppl):1263–1269. doi: 10.1016/0002-9394(67)94108-6. [DOI] [PubMed] [Google Scholar]
- Newhall W. J., Batteiger B., Jones R. B. Analysis of the human serological response to proteins of Chlamydia trachomatis. Infect Immun. 1982 Dec;38(3):1181–1189. doi: 10.1128/iai.38.3.1181-1189.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nichols R. L., Murray E. S., Nisson P. E. Use of enteric vaccines in protection against chlamydial infections of the genital tract and the eye of guinea pigs. J Infect Dis. 1978 Dec;138(6):742–746. doi: 10.1093/infdis/138.6.742. [DOI] [PubMed] [Google Scholar]
- Nichols R. L., Oertley R. E., Fraser E. C., MacDonald A. B., McComb D. E. Immunity to chlamydial infections of the eye. VI. Homologous neutralization of trachoma infectivity for the owl monkey conjuctivae by eye secretions from humans with trachoma. J Infect Dis. 1973 Apr;127(4):429–432. doi: 10.1093/infdis/127.4.429. [DOI] [PubMed] [Google Scholar]
- Pavia C. S., Schachter J. Failure to detect cell-mediated cytotoxicity against Chlamydia trachomatis-infected cells. Infect Immun. 1983 Mar;39(3):1271–1274. doi: 10.1128/iai.39.3.1271-1274.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qvigstad E., Hirschberg H. Lack of cell-mediated cytotoxicity towards Chlamydia trachomatis infected target cells in humans. Acta Pathol Microbiol Immunol Scand C. 1984 Jun;92(3):153–159. doi: 10.1111/j.1699-0463.1984.tb00067.x. [DOI] [PubMed] [Google Scholar]
- Ramsey K. H., Newhall W. J., 5th, Rank R. G. Humoral immune response to chlamydial genital infection of mice with the agent of mouse pneumonitis. Infect Immun. 1989 Aug;57(8):2441–2446. doi: 10.1128/iai.57.8.2441-2446.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Rank R. G. Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines. Infect Immun. 1991 Mar;59(3):925–931. doi: 10.1128/iai.59.3.925-931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramsey K. H., Soderberg L. S., Rank R. G. Resolution of chlamydial genital infection in B-cell-deficient mice and immunity to reinfection. Infect Immun. 1988 May;56(5):1320–1325. doi: 10.1128/iai.56.5.1320-1325.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Barron A. L. Humoral immune response in acquired immunity to chlamydial genital infection of female guinea pigs. Infect Immun. 1983 Jan;39(1):463–465. doi: 10.1128/iai.39.1.463-465.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Barron A. L. Specific effect of estradiol on the genital mucosal antibody response in chlamydial ocular and genital infections. Infect Immun. 1987 Sep;55(9):2317–2319. doi: 10.1128/iai.55.9.2317-2319.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Batteiger B. E., Soderberg L. S. Susceptibility to reinfection after a primary chlamydial genital infection. Infect Immun. 1988 Sep;56(9):2243–2249. doi: 10.1128/iai.56.9.2243-2249.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Soderberg L. S., Barron A. L. Chronic chlamydial genital infection in congenitally athymic nude mice. Infect Immun. 1985 Jun;48(3):847–849. doi: 10.1128/iai.48.3.847-849.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., Soderberg L. S., Sanders M. M., Batteiger B. E. Role of cell-mediated immunity in the resolution of secondary chlamydial genital infection in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis. Infect Immun. 1989 Mar;57(3):706–710. doi: 10.1128/iai.57.3.706-710.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rank R. G., White H. J., Barron A. L. Humoral immunity in the resolution of genital infection in female guinea pigs infected with the agent of guinea pig inclusion conjunctivitis. Infect Immun. 1979 Nov;26(2):573–579. doi: 10.1128/iai.26.2.573-579.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schachter J. Chlamydial infections (first of three parts). N Engl J Med. 1978 Feb 23;298(8):428–435. doi: 10.1056/NEJM197802232980805. [DOI] [PubMed] [Google Scholar]
- Schachter J. Chlamydial infections (second of three parts). N Engl J Med. 1978 Mar 2;298(9):490–495. doi: 10.1056/NEJM197803022980905. [DOI] [PubMed] [Google Scholar]
- Schachter J. Chlamydial infections (third of three parts). N Engl J Med. 1978 Mar 9;298(10):540–549. doi: 10.1056/NEJM197803092981005. [DOI] [PubMed] [Google Scholar]
- Schachter J., Cles L. D., Ray R. M., Hesse F. E. Is there immunity to chlamydial infections of the human genital tract? Sex Transm Dis. 1983 Jul-Sep;10(3):123–125. doi: 10.1097/00007435-198307000-00004. [DOI] [PubMed] [Google Scholar]
- Starnbach M. N., Bevan M. J., Lampe M. F. Protective cytotoxic T lymphocytes are induced during murine infection with Chlamydia trachomatis. J Immunol. 1994 Dec 1;153(11):5183–5189. [PubMed] [Google Scholar]
- Su H., Caldwell H. D. CD4+ T cells play a significant role in adoptive immunity to Chlamydia trachomatis infection of the mouse genital tract. Infect Immun. 1995 Sep;63(9):3302–3308. doi: 10.1128/iai.63.9.3302-3308.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tuffrey M., Falder P., Taylor-Robinson D. Effect on Chlamydia trachomatis infection of the murine genital tract of adoptive transfer of congenic immune cells or specific antibody. Br J Exp Pathol. 1985 Aug;66(4):427–433. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Wagar E. A., Schachter J., Bavoil P., Stephens R. S. Differential human serologic response to two 60,000 molecular weight Chlamydia trachomatis antigens. J Infect Dis. 1990 Oct;162(4):922–927. doi: 10.1093/infdis/162.4.922. [DOI] [PubMed] [Google Scholar]
- Wang S. P., Grayston J. T., Alexander E. R. Trachoma vaccine studies in monkeys. Am J Ophthalmol. 1967 May;63(5 Suppl):1615–1630. doi: 10.1016/0002-9394(67)94155-4. [DOI] [PubMed] [Google Scholar]
- Watson R. R., Mull J. D., MacDonald A. B., Thompson S. E., 3rd, Bear S. E. Immunity to chlamydial infections of the eye. II. Studies of passively transferred serum antibody in resistance to infection with guinea pig inclusion conjunctivitis. Infect Immun. 1973 Apr;7(4):597–599. doi: 10.1128/iai.7.4.597-599.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams D. M., Grubbs B., Schachter J. Primary murine Chlamydia trachomatis pneumonia in B-cell-deficient mice. Infect Immun. 1987 Oct;55(10):2387–2390. doi: 10.1128/iai.55.10.2387-2390.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams D. M., Magee D. M., Bonewald L. F., Smith J. G., Bleicker C. A., Byrne G. I., Schachter J. A role in vivo for tumor necrosis factor alpha in host defense against Chlamydia trachomatis. Infect Immun. 1990 Jun;58(6):1572–1576. doi: 10.1128/iai.58.6.1572-1576.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams D. M., Schachter J., Grubbs B., Sumaya C. V. The role of antibody in host defense against the agent of mouse pneumonitis. J Infect Dis. 1982 Feb;145(2):200–205. doi: 10.1093/infdis/145.2.200. [DOI] [PubMed] [Google Scholar]
- Williams D. M., Schachter J., Weiner M. H., Grubbs B. Antibody in host defense against mouse pneumonitis agent (murine Chlamydia trachomatis). Infect Immun. 1984 Sep;45(3):674–678. doi: 10.1128/iai.45.3.674-678.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woolridge R. L., Grayston J. T., Chang I. H., Yang C. Y., Cheng K. H. Long-term follow-up of the initial (1959-1960) trachoma vaccine field trial on Taiwan. Am J Ophthalmol. 1967 May;63(5 Suppl):1650–1655. doi: 10.1016/0002-9394(67)94159-1. [DOI] [PubMed] [Google Scholar]
- 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]
