Determinants of Chlamydial Pathogenesis and Immunity

Patrik M. Bavoil

doi:10.1128/9781555818340.ch19

Chapter 19 : Determinants of Chlamydial Pathogenesis and Immunity

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Department of Microbiology and Immunology, University of Rochester Medical Center, Box 672, Rochester, New York 14642

Content Type: Monograph

Publication Year: 1994

Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis

Book DOI: 10.1128/9781555818340

Chapter DOI: 10.1128/9781555818340.ch19

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Determinants of Chlamydial Pathogenesis and Immunity, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818340/9781555810825_Chap19-1.gif /docserver/preview/fulltext/10.1128/9781555818340/9781555810825_Chap19-2.gif

Abstract:

This chapter focuses on the molecular determinants of the initial step of chlamydial pathogenesis, adherence, and on the antigens responsible for immunopathogenesis and immunity to chlamydial infection. Three equally tangible reasons to be pessimistic are that (i) natural immunity is of short duration, (ii) there may be more, or less, to hypersensitivity than Hsp-60, and (iii) various synthetic or recombinant major outer membrane protein (MOMP)-based immunization regimens have so far failed to generate significant protection against either infection or pathology. In this system, parenteral immunization with live elementary bodies (EBs), UV-inactivated EBs, or MOMP-enriched extracts all elicited protective immunity, albeit to various degrees, in the female genital tract. First, it is not clear that Hsp-60 is solely responsible for eliciting DTH; i.e., other deleterious chlamydial antigens may exist. Second, the original experiments performed by Watkins and coworkers and Morrison and coworkers included Triton X-100 in the Hsp-60 preparations. Third, it is unclear what role other contaminants of the preparations may have played in the observed immunopathologies; in this regard, it is worrisome that the recombinant Hsp-60 used in the experiments of Morrison and coworkers appeared to be contaminated with significant quantities of endotoxin. Lastly, in reverse experiments in which guinea pigs were primed with sucrose gradient-purified Hsp-60 and challenged in the eye with live GPIC organisms, enhanced immunopathology was not observed. The development of methods of genetic transfer for Chlamydia species presents unique challenges.

Citation: Bavoil P. 1994. Determinants of Chlamydial Pathogenesis and Immunity, p 295-308. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch19

Key Concept Ranking

Infection and Immunity: 0.69694376
Outer Membrane Proteins: 0.6049579
Immune Systems: 0.5035548
Cell-Mediated Immune Response: 0.4731953

0.69694376

Highlighted Text: Show | Hide

Full text loading...

Figures

Determinants of Chlamydial Pathogenesis and Immunity

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555818340.chap19-1,webId=/content/author/10.1128/9781555818340.chap19-1,properties={foaf_givenname=Patrik M., foaf_name=Patrik M. Bavoil, foaf_surname=Bavoil, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555818340.chap19-aff1]]}]]

/content/10.1128/9781555818340.chap19.fig19-1

Figure 1

A reductionist view of the chlamydial life cycle. At time zero, the infectious EB is internalized and subsequently differentiates into the metabolically active RB. At time 24 to 40+ h, RBs differentiate back to EBs. Two classes of proteins are central to the latter differentiation event: (i) cysteine-rich proteins, including the constitutively expressed MOMI and the late-expressed Omp-2 and Omp-3 proteins, which form disulfide bonds rendering the outer cell wall rigid and impermeable ( 8 ), and (ii) histone-like proteins which likely mediate chromosomal condensation ( 5 ).

10.1128/9781555818340/fig19-1_thmb.gif

10.1128/9781555818340/fig19-1.gif

Figure 1

/content/10.1128/9781555818340.chap19.fig19-2

Figure 2

Receptor-mediated attachment of C. trachomatis EBs to McCoy cells (reproduced with permission from P. B. Wyrick and reference 19 ). Electron micrographs show EBs tightly attached at the base of microvilli (Mv) and in clathrin-coated pits (arrows). Bars, 0.1 µm.

10.1128/9781555818340/fig19-2_thmb.gif

10.1128/9781555818340/fig19-2.gif

Figure 2

References

/content/book/10.1128/9781555818340.chap19

1. Allen, J. E.,, M. C. Cerrone,, P. R. Beatty,, and R. S. Stephens. 1990. Cysteine-rich outer membrane proteins of Chlamydia trachomatis display compensatory sequence changes between biovariants. Mol. Microbiol. 4: 1543– 1550.

2. Allen, J. E.,, R. M. Locksley,, and R. S. Stephens. 1991. A single peptide from the major outer membrane protein of Chlamydia trachomatis elicits T cell help for the production of antibodies to protective determinants. J. Immunol. 147: 674– 679.

3. Allen, J. E.,, and R. S. Stephens. 1989. Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2. J. Bacteriol. 171: 285– 291.

4. Barnes, R. C.,, B. P. Katz,, R. T. Rolfs,, B. E. Batteiger,, V. Caine,, and R. B. Jones. 1990. Quantitative culture of endocervical Chlamydia trachomatis. J. Clin. Microbiol. 28: 774– 780.

5. Barry, C. E., III,, S. F. Hayes,, and T. Hackstadt. 1992. Nucleoid condensation in Escherichia coli that express a chlamydial histone homolog. Science 256: 377– 378.

6. Batteiger, B. E.,, W. J. Newhall,, and R. B. Jones. 1985. Differences in outer membrane proteins of the lymphogranuloma venereum and trachoma biovars of Chlamydia trachomatis. Infect. Immun. 50: 488– 494.

7. Batteiger, B. E.,, R. G. Rank,, P. M. Bavoil,, and L. S. F. Soderberg. 1993. Partial protection against genital reinfection by immunization of guinea pigs with isolated outer membrane proteins of the chlamydial agent of guinea pig inclusion conjunctivitis. J. Gen. Microbiol. 139: 2965– 2972.

8. Bavoil, P. M.,, A. Ohlin,, and J. Schachter. 1984. Role of disulfide bonding in outer membrane structure and permeability in Chlamydia trachomatis. Infect. Immun. 44: 479– 485.

9. Bavoil, P. M.,, and R. G. Rank. Unpublished data.

10. Caldwell, H. D.,, J. Kromhout,, and J. Schachter. 1981. Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect. Immun. 31: 1161– 1176.

11.Centers for Disease Control. 1982. Prevention of blindness: trachoma control. Morbid. Mortal. Weekly Rep. 31: 561– 562.

12. Centers for Disease Control and Prevention. 1993. Recommendations for the prevention and management of Chlamydia trachomatis infections. Morbid. Mortal. Weekly Rep. 42( RR-12): l– 39.

13. Collett, B. A.,, W. J. Newhall,, R. A. Jersild, Jr.,, and R. B. Jones. 1989. Detection of surface-exposed epitopes on Chlamydia trachomatis by immune electron microscopy. J. Gen. Microbiol. 135: 85– 94.

14. Danilition, S. L.,, I. W. Maclean,, R. Peeling,, S. Winston,, and R. C. Brunham. 1990. The 75-kilodalton protein of Chlamydia trachomatis: a member of the heat shock protein 70 family. Infect. Immun. 58: 189– 196.

15. Everett, K. D.,, and T. P. Hatch. 1991. Sequence analysis and lipid modification of the cysteine-rich envelope proteins of Chlamydia psittaci 6BC. J. Bacteriol. 173: 3821– 3830.

16. Hackstadt, T.,, W. Baehr,, and Y. Ying. 1991. Chlamydia trachomatis developmentally regulated protein is homologous to eukaryotic histone HI. Proc. Natl. Acad. Sci. USA 88: 3937– 3941.

17. Hatch, T. P.,, I. Allan,, and J. H. Pearce. 1984. Structural and polypeptide differences between envelopes of infective and reproductive life cycle forms of Chlamydia spp. J. Bacteriol. 157: 13– 20.

18. Hatch, T. P.,, M. Miceli,, and J. E. Sublett. 1986. Synthesis of disulfide-bonded outer membrane proteins during the developmental cycle of Chlamydia psittaci and Chlamydia trachomatis. J. Bacteriol. 165: 379– 385.

19. Hodinka, R. L.,, C. H. Davis,, J. Choong,, and P. B. Wyrick. 1988. Ultrastructural study of endocyto-sis of Chlamydia trachomatis by McCoy cells. Infect. lmmun. 56: 1456– 1463.

20. Hodinka, R. L.,, and P. B. Wyrick. 1986. Ultrastructural study of mode of entry of Chlamydia psittaci into L-929 cells. Infect. lmmun. 54: 855– 863.

21. Jacobs, W. R., Jr.,, G. V. Kalpana,, J. D. Cirillo,, L. Pascopella,, S. B. Snapper,, R. A. Udani,, W. Jones,, R. G. Barletta,, and B. R. Bloom. 1991. Genetic systems for mycobacteria. Methods Enzymol. 204: 537– 555.

22. Joseph, T. D.,, and S. K. Bose. 1991. A heat-labile protein of Chlamydia trachomatis binds to HeLa cells and inhibits the adherence of chlamydiae. Proc. Natl. Acad. Sci. USA 88: 4054– 4058.

23. Katz, B. P.,, B. E. Batteiger,, and R. B. Jones. 1987. Effect of prior sexually transmitted disease on the isolation of Chlamydia trachomatis. Sex. Transm. Dis. 14: 160– 164.

24. Kunimoto, D.,, and R. C. Brunham. 1985. Human immune response and Chlamydia trachomatis infection. Rev. Infect. Dis. 7: 665– 673.

25. Langer, T.,, C. Lu,, H. Echols,, J. Flanagan,, M. K. Hayer,, and F. U. Hartl. 1992. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature (London) 356: 683– 689.

26. Masson, P. L.,, J. F. Heremans,, and J. Ferin. 1969. Clinical importance of the biochemical changes in the female genital tract. I. Studies on the proteins of the cervical mucus. Int. J. Fértil. 14: 1– 7.

27. Morrison, R. P. 1991. Chlamydial hsp60 and the immunopathogenesis of chlamydial disease. Semin. Immunol. 3: 25– 33.

28. Morrison, R. P.,, R. J. Belland,, K. Lyng,, and H. D. Caldwell. 1989. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J. Exp. Med. 170: 1271– 1283.

29. Morrison, R. P.,, K. Lyng,, and H. D. Caldwell. 1989. Chlamydial disease pathogenesis. Ocular hypersensitivity elicited by a genus-specific 57-kD protein. J. Exp. Med. 169: 663– 675.

30. Morrison, R. P.,, D. S. Manning,, and H. D. Caldwell,. 1992. Immunology of Chlamydia trachomatis infections: immunoprotective and immunopathogenetic responses, p. 57– 84. In T. C. Quinn (ed.), Sexually Transmitted Diseases. Raven Press Ltd., New York.

31. Moulder, J. W. 1991. Interaction of chlamydiae and host cells in vitro. Microbiol. Rev. 55: 143– 190.

32. Mount, D. T.,, P. E. Bigazzi,, and A. L. Barron. 1972. Infection of genital tract and transmission of ocular infection to newborns by the agent of guinea pig inclusion conjunctivitis. Infect. lmmun. 5: 921– 926.

33. Murdin, A. D.,, H. Su,, D. S. Manning,, M. H. Klein,, M. J. Parnell,, and H. D. Caldwell. 1993. A poliovirus hybrid expressing a neutralization epitope from the major outer membrane protein of Chlamydia trachomatis is highly immunogenic. Infect. lmmun. 61: 4406– 4414.

34. Murray, E. S. 1964. Guinea pig inclusion conjunctivitis. I. Isolation and identification as a member of the psittacosis-lymphogranuloma-trachoma group. J. Infect. Dis. 114: 1– 12.

35. Newhall, W. J. 1987. Biosynthesis and disulfide cross-linking of outer membrane components during the growth cycle of Chlamydia trachomatis. Infect. lmmun. 55: 162– 168.

36. Newhall, W. J.,, and R. B. Jones. 1983. Disulfide linked oligomers of the major outer membrane protein of chlamydiae. J. Bacteriol. 154: 998– 1001.

37. Palmer, L.,, and S. Falkow. 1986. A common plasmid of Chlamydia trachomatis. Plasmid 16: 52– 62.

38. Ramsey, K. H.,, and R. G. Rank. 1991. Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines. Infect. lmmun. 59: 925– 931.

39. Ramsey, K. H.,, L. S. F. Soderberg,, and R. G. Rank. 1988. Resolution of chlamydial genital infection in B-cell-deficient mice and immunity to reinfection. Infect. lmmun. 56: 1320– 1325.

40. Rank, R. G.,, and A. L. Barron. 1983. Effect of antithymocyte serum on the course of chlamydial genital infection in female guinea pigs. Infect. lmmun. 41: 876– 879.

41. Rank, R. G.,, and B. E. Batteiger. 1989. Protective role of serum antibody in immunity to chlamydial genital infection. Infect. Immun. 57: 299– 301.

42. Rank, R. G.,, B. E. Batteiger,, and L. S. F. Soderberg. 1988. Susceptibility to reinfection after a primary chlamydial genital infection. Infect. Immun. 56: 2243– 2249.

43. Rank, R. G.,, B. E. Batteiger,, and L. S. F. Soderberg. 1990. Immunization against chlamydial genital infection in guinea pigs with UV-inactivated and viable chlamydiae administered by different routes. Infect. Immun. 58: 2599– 2605.

44. Rank, R. G.,, and P. M. Bavoil. Unpublished data.

45. Rank, R. G.,, and M. M. Sanders,. 1990. Ascending genital tract infection as a common consequence of vaginal inoculation with the guinea pig inclusion conjunctivitis agent in normal guinea pigs, p. 249– 252. In W. R. Bowie,, H. D. Caldwell,, R. B. Jones,, P.-A. Mardh,, G. L. Ridgway,, J. Schachter,, W. E. Stamm,, and M. E. Ward (ed.), Chlamydial Infections. Cambridge University Press, New York.

46. Rank, R. G.,, L. S. F. Soderberg,, and A. L. Barron. 1985. Chronic chlamydial genital infection in congenitally athymic nude mice. Infect. Immun. 48: 847– 849.

47. Rank, R. G.,, H. J. White,, and A. L. Barron. 1979. Humoral immunity in the resolution of genital infection in female guinea pigs infected with the agent of guinea pig inclusion conjunctivitis. Infect. Immun. 26: 573– 579.

48. Raulston, J. E.,, C. H. Davis,, D. H. Schmiel,, M. W. Morgan,, and P. B. Wyrick. 1993. Molecular characterization and outer membrane association of a Chlamydia trachomatis protein related to the hsp70 family of proteins. J. Biol. Chem. 268: 23139– 23147.

49. Reynolds, D. J.,, and J. H. Pearce. 1991. Endocytic mechanisms utilized by chlamydiae and their influence on induction of productive infection. Infect. Immun. 59: 3033– 3039.

50. Schachter, J. 1989. Pathogenesis of chlamydial infections. Pathol. Immunopathol. Res. 8: 206– 220.

51. Schachter, J.,, and C. R. Dawson. 1978. Human Chlamydial Infections. PSG Publishing Company, Inc., Littleton, Mass..

52. Schmiel, D. H.,, S. T. Knight,, J. E. Raulston,, J. Choong,, C. H. Davis,, and P. B. Wyrick. 1991. Recombinant Escherichia coli clones expressing Chlamydia trachomatis gene products attach to human endometrial epithelial cells. Infect. Immun. 59: 4001– 4012.

53. Soldat!, D.,, and J. C. Boothroyd. 1993. Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii. Science 260: 349– 352.

54. Stephens, R. S. 1993. Challenge of Chlamydia research. Infect. Agents Dis. 1: 279– 293.

55. Stephens, R. S.,, G. Mullenbach,, R. Sanchez-Pescador,, and N. Agabian. 1986. Sequence analysis of the major outer membrane protein gene from Chlamydia trachomatis serovar L2. J. Bacteriol. 168: 1277– 1282.

56. Stephens, R. S.,, R. Shanchez-Pescador,, E. A. Wagar,, C. Inouye,, and M. S. Urdea. 1987. Diversity of Chlamydia trachomatis major outer membrane protein genes. J. Bacteriol. 169: 3879– 3885.

57. Su, H.,, and H. D. Caldwell. 1992. Immunogenicity of a chimeric peptide corresponding to T helper and T cell epitopes of the Chlamydia trachomatis major outer membrane protein. J. Exp. Med. 175: 227– 235.

58. Su, H.,, and H. D. Caldwell. 1993. Immunogenicity of a synthetic oligopeptide corresponding to antigenically common T-helper and B-cell neutralizing epitopes of the major outer membrane protein of Chlamydia trachomatis. Vaccine 11: 1159– 1166.

59. Su, H.,, R. P. Morrison,, N. G. Watkins,, and H. D. Caldwell. 1990. Identification and characterization of T helper cell epitopes of the major outer membrane protein of Chlamydia trachomatis. J. Exp. Med, 172: 203– 212.

60. Su, H.,, N. G. Watkins,, Y.-X. Zhang,, and H. D. Caldwell. 1990. Chlamydia trachomatis-host cell interactions: role of the chlamydial major outer membrane protein as an adhesin. Infect. Immun. 58: 1017– 1025.

61. Su, H.,, Y.-X. Zhang,, O. Barrera,, N. G. Watkins,, and H. D. Caldwell. 1988. Differential effect of trypsin on infectivity of Chlamydia trachomatis: loss of infectivity requires cleavage of major outer membrane protein variable domains II and IV. Infect. Immun. 56: 2094– 2100.

62. Tam, J. E.,, S. T. Knight,, C. H. Davis,, and P. B. Wyrick. 1992. Eukaryotic cells grown on microcarrier beads offer a cost-efficient way to propagate Chlamydia trachomatis. BioTechniques 13: 374– 378.

63. Ting, L.-M.,, and P. M. Bavoil. Unpublished data.

64. Ward, M. E. 1992. Chlamydia vaccines—future trends. J. Infect. 25: S11– S26.

65. Watkins, N. G.,, W. J. Hadlow,, A. B. Moos,, and H. D. Caldwell. 1986. Ocular delayed hypersensitivity: a pathogenetic mechanism of chlamydial conjunctivitis in guinea pigs. Proc. Natl. Acad. Sci. USA 83: 7480– 7484.

66. Witkin, S. S.,, J. Jeremías,, M. Toth,, and W. J. Ledger. 1993. Cell-mediated immune response to the recombinant 57-kDa heat-shock protein of Chlamydia trachomatis in women with salpingitis. J. Infect. Dis. 167: 1379– 1383.

67. Yuan, Y.,, Y.-X. Zhang,, N. G. Watkins,, and H. D. Caldwell. 1989. Nucleotide and deduced amino acid sequences for the four variable domains of the major outer membrane proteins of the 15 Chlamydia trachomatis serovars. Infect. Immun. 57: 1040– 1049.

68. Zhang, J. P.,, and R. S. Stephens. 1992. Mechanism of Chlamydia trachomatis attachment to eukaryotic host cells. Cell 69: 861– 869.

69. Zhang, Y. X.,, S. Stewart,, T. Joseph,, H. R. Taylor,, and H. D. Caldwell. 1987. Protective monoclonal antibodies recognize epitopes located on the major outer membrane protein of Chlamydia trachomatis. J. Immunol. 138: 575– 581.