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. 1996 Jun;64(6):2300–2307. doi: 10.1128/iai.64.6.2300-2307.1996

A model of genital Chlamydia trachomatis infection using human xenografts in severe combined immunodeficiency mice.

A Essig 1, A Rudolphi 1, M Heinemann 1, H Rosenthal 1, R Kaufmann 1, J Reimann 1, R Marre 1
PMCID: PMC174070  PMID: 8675341

Abstract

We developed a new model of human genital Chlamydia trachomatis infection in order to characterize the pathogen-host relationship in a clinically relevant system using a human strain of C. trachomatis instead of the commonly employed mouse biovar (MoPn). Human endometrial tissue was xenografted into the skin of mice homozygous for the mutation severe combined immunodeficiency and inoculated with C. trachomatis serovar K. C. trachomatis efficiently infected the endometrium as shown by cell culture and immunofluorescence microscopy and persisted for more than 6 weeks. Chlamydial inclusions detected by direct immunofluorescence and electron microscopy appeared to be smaller than those produced by in vitro cell culture-grown chlamydiae. A pattern of localized mild infection prevailed, and infiltrative uncontrolled spread of chlamydiae was observed in only 1 of 10 infected grafts. This might correspond to the well-known tendency of the agent to cause asymptomatic infections. This model allows the study of a human genital infection resembling the clinical situation and offers the possibility to better characterize the host-parasite relationship with respect to pathogenicity and therapy.

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Selected References

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  1. Arno J. N., Ricker V. A., Batteiger B. E., Katz B. P., Caine V. A., Jones R. B. Interferon-gamma in endocervical secretions of women infected with Chlamydia trachomatis. J Infect Dis. 1990 Dec;162(6):1385–1389. doi: 10.1093/infdis/162.6.1385. [DOI] [PubMed] [Google Scholar]
  2. Barron A. L., Rank R. G., Moses E. B. Immune response in mice infected in the genital tract with mouse pneumonitis agent (Chlamydia trachomatis biovar). Infect Immun. 1984 Apr;44(1):82–85. doi: 10.1128/iai.44.1.82-85.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barron A. L., White H. J., Rank R. G., Soloff B. L., Moses E. B. A new animal model for the study of Chlamydia trachomatis genital infections: infection of mice with the agent of mouse pneumonitis. J Infect Dis. 1981 Jan;143(1):63–66. doi: 10.1093/infdis/143.1.63. [DOI] [PubMed] [Google Scholar]
  4. Beatty W. L., Byrne G. I., Morrison R. P. Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998–4002. doi: 10.1073/pnas.90.9.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beatty W. L., Morrison R. P., Byrne G. I. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev. 1994 Dec;58(4):686–699. doi: 10.1128/mr.58.4.686-699.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beatty W. L., Morrison R. P., Byrne G. I. Reactivation of persistent Chlamydia trachomatis infection in cell culture. Infect Immun. 1995 Jan;63(1):199–205. doi: 10.1128/iai.63.1.199-205.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blander S. J., Amortegui A. J. Mice immunized with a chlamydial extract have no increase in early protective immunity despite increased inflammation following genital infection by the mouse pneumonitis agent of Chlamydia trachomatis. Infect Immun. 1994 Sep;62(9):3617–3624. doi: 10.1128/iai.62.9.3617-3624.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bosma M. J., Carroll A. M. The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol. 1991;9:323–350. doi: 10.1146/annurev.iy.09.040191.001543. [DOI] [PubMed] [Google Scholar]
  9. Caldwell H. D., Kromhout J., Schachter J. Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1981 Mar;31(3):1161–1176. doi: 10.1128/iai.31.3.1161-1176.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Campbell S., Richmond S. J., Haynes P., Gump D., Yates P., Allen T. D. An in vitro model of Chlamydia trachomatis infection in the regenerative phase of the human endometrial cycle. J Gen Microbiol. 1988 Jul;134(7):2077–2087. doi: 10.1099/00221287-134-7-2077. [DOI] [PubMed] [Google Scholar]
  11. Fu Y., Baumann M., Kosma P., Brade L., Brade H. A synthetic glycoconjugate representing the genus-specific epitope of chlamydial lipopolysaccharide exhibits the same specificity as its natural counterpart. Infect Immun. 1992 Apr;60(4):1314–1321. doi: 10.1128/iai.60.4.1314-1321.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Jantos C., Baumgärtner W., Durchfeld B., Schiefer H. G. Experimental epididymitis due to Chlamydia trachomatis in rats. Infect Immun. 1992 Jun;60(6):2324–2328. doi: 10.1128/iai.60.6.2324-2328.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaufmann R., Mielke V., Reimann J., Klein C. E., Sterry W. Cellular and molecular composition of human skin in long-term xenografts on SCID mice. Exp Dermatol. 1993 Oct;2(5):209–216. doi: 10.1111/j.1600-0625.1993.tb00035.x. [DOI] [PubMed] [Google Scholar]
  15. Kaufmann R., Rudolphi A., Boxberger H. J., Hainzl A., Rosenthal H., Reimann J. Stable engraftment of human female genital mucous membrane xenografts on SCID mice. Gynecol Obstet Invest. 1995;40(2):97–100. doi: 10.1159/000292314. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Maslow A. S., Davis C. H., Choong J., Wyrick P. B. Estrogen enhances attachment of Chlamydia trachomatis to human endometrial epithelial cells in vitro. Am J Obstet Gynecol. 1988 Oct;159(4):1006–1014. doi: 10.1016/s0002-9378(88)80189-3. [DOI] [PubMed] [Google Scholar]
  18. Mayer J., Woods M. L., Vavrin Z., Hibbs J. B., Jr Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells. Infect Immun. 1993 Feb;61(2):491–497. doi: 10.1128/iai.61.2.491-497.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McDermott M. R., Clark D. A., Bienenstock J. Evidence for a common mucosal immunologic system. II. Influence of the estrous cycle on B immunoblast migration into genital and intestinal tissues. J Immunol. 1980 Jun;124(6):2536–2539. [PubMed] [Google Scholar]
  20. Moorman D. R., Sixbey J. W., Wyrick P. B. Interaction of Chlamydia trachomatis with human genital epithelium in culture. J Gen Microbiol. 1986 Apr;132(4):1055–1067. doi: 10.1099/00221287-132-4-1055. [DOI] [PubMed] [Google Scholar]
  21. Moulder J. W. Interaction of chlamydiae and host cells in vitro. Microbiol Rev. 1991 Mar;55(1):143–190. doi: 10.1128/mr.55.1.143-190.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Patton D. L., Kuo C. C., Brenner R. M. Chlamydia trachomatis oculogenital infection in the subcutaneous autotransplant model of conjunctiva, salpinx and endometrium. Br J Exp Pathol. 1989 Jun;70(3):357–367. [PMC free article] [PubMed] [Google Scholar]
  23. Rank R. G., Sanders M. M. Pathogenesis of endometritis and salpingitis in a guinea pig model of chlamydial genital infection. Am J Pathol. 1992 Apr;140(4):927–936. [PMC free article] [PubMed] [Google Scholar]
  24. Raulston J. E. Chlamydial envelope components and pathogen-host cell interactions. Mol Microbiol. 1995 Feb;15(4):607–616. doi: 10.1111/j.1365-2958.1995.tb02370.x. [DOI] [PubMed] [Google Scholar]
  25. Shemer-Avni Y., Wallach D., Sarov I. Inhibition of Chlamydia trachomatis growth by recombinant tumor necrosis factor. Infect Immun. 1988 Sep;56(9):2503–2506. doi: 10.1128/iai.56.9.2503-2506.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sweet R. L., Blankfort-Doyle M., Robbie M. O., Schacter J. The occurrence of chlamydial and gonococcal salpingitis during the menstrual cycle. JAMA. 1986 Apr 18;255(15):2062–2064. [PubMed] [Google Scholar]
  27. Weiss E., Schramek S., Wilson N. N., Newman L. W. Deoxyribonucleic Acid Heterogeneity Between Human and Murine Strains of Chlamydia trachomatis. Infect Immun. 1970 Jul;2(1):24–28. doi: 10.1128/iai.2.1.24-28.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Williams D. M., Grubbs B. G., Schachter J., Magee D. M. Gamma interferon levels during Chlamydia trachomatis pneumonia in mice. Infect Immun. 1993 Aug;61(8):3556–3558. doi: 10.1128/iai.61.8.3556-3558.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Wyrick P. B., Choong J., Davis C. H., Knight S. T., Royal M. O., Maslow A. S., Bagnell C. R. Entry of genital Chlamydia trachomatis into polarized human epithelial cells. Infect Immun. 1989 Aug;57(8):2378–2389. doi: 10.1128/iai.57.8.2378-2389.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zhong G. M., Peterson E. M., Czarniecki C. W., Schreiber R. D., de la Maza L. M. Role of endogenous gamma interferon in host defense against Chlamydia trachomatis infections. Infect Immun. 1989 Jan;57(1):152–157. doi: 10.1128/iai.57.1.152-157.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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