Determinants of Chlamydial Pathogenesis and Immunity

Patrik M. Bavoil

doi:10.1128/9781555818340.ch19

Chapter 19 : Determinants of Chlamydial Pathogenesis and Immunity

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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

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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

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Determinants of Chlamydial Pathogenesis and Immunity

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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 ).

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Figure 1

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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.

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