Chlamydia trachomatis: Its Role in Tubal Infertility

Brunham, Robert C.; Maclean, Ian; Binns, B. A. O.; Peeling, Rosanna W.

doi:10.1093/infdis/152.6.1275

Cited by 241 publications

(113 citation statements)

References 18 publications

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“…Further, the cysteine-rich nature of this protein and its expression late in the developmental cycle suggest involvement in the disul- fide-mediated changes that are essential for the switch between intracellular and extracellular stages of this organism (4,9). The antigenic significance of this protein in the host immune response is demonstrated by studies in which the presence of antibodies to OMP2 is consistently observed in active infection (5,8,21) and is correlated with disease status (5,6,11). Although no differences in antigenicity have been observed between the OMP2s of trachoma and LGV biovars (3,20), significant differences in physical (20) and chemical (3) properties of this protein between biovars have been reported.…”

Section: Resultsmentioning

confidence: 99%

Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2

Allen

Stephens

1989

J Bacteriol

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The 60,000-molecular-weight cysteine-rich outer membrane protein (OMP2) from Chiamydia trachomatis participates in the disulfide-mediated outer-membrane organization unique to this organism. In addition, this protein is a primary focus of the host immune response. We cloned and sequenced the gene Infections by Chlamydia trachomatis are a leading cause of sexually transmitted disease, infertility, and blindness. Within the species, two biovars have been described which are responsible for human disease (19). The trachoma biovar infects mucosal epithelial cells and produces localized infection of the urogenital tract and eyes. The lymphogranuloma venereum (LGV) biovar has broader host cell specificity and causes more invasive sexually transmitted disease. Chlamydiae have a unique life cycle in which the bacteria alternate between two developmental forms, the extracellular elementary body (EB) and the intracellular reticulate body. Only the EB is capable of extracellular survival, host cell recognition, and invasion, suggesting a fundamental role for EB outer membrane constituents in infectivity.The differences in infectivity observed between the trachoma and LGV biovars may be mediated by dissimilarity in outer membrane composition, variation in primary structure of the EB constituents, or higher-ordered structural heterogeneity. The EB outer membrane contains three cysteinerich proteins with molecular weights of about 40,000 (MOMP), 60,000 (OMP2), and 15,000. The chlamydial cell envelope lacks a peptidoglycan layer for structural integrity (2). It has been proposed that in its absence inter-and intramolecular disulfide bonding among the cysteine-rich proteins imparts rigidity to the EB outer membrane (22).Complete sequence information for the MOMP-encoding genes of several serotypes (25,26) indicates that this protein is antigenically complex, possessing species-, subspeciesand serovar-specific epitopes on each molecule (28). The 15,000-molecular-weight cysteine-rich protein has recently been described as possessing both biovar-and speciesspecific epitopes (31). To date, the epitopes identified on the 60,000-molecular-weight outer-membrane protein by monoclonal antibodies have all been species specific, demonstrating less antigenic diversity than the other cysteine-rich proteins (20). * Corresponding author.Despite the evidence for a shared antigenic structure, there are several striking physical differences between the 60,000-molecular-weight proteins of the trachoma biovar and the more invasive LGV biovar. This protein appears as a predominant single band in gel electrophoresis of trachoma strains but is present as a less intense doublet in LGV strains (3). Recently, peptide maps have demonstrated that there are significant structural differences between the proteins of these two biovars (20). Further, it has been observed that the 60,000-molecular-weight protein of the trachoma biovar has a nearly neutral isoelectric point (pl), whereas the LGV proteins have a net positive charge, with a pl of 8.5 to 9.0 (3)...

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Section: Resultsmentioning

confidence: 99%

Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2

Allen

Stephens

1989

J Bacteriol

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“…Repeated or persistent infection appears to underlay much of the tissue-damaging effects of infection and can lead to infertility and blindness (1)(2)(3)(4). Because of the public health importance of chlamydial diseases, there has been long-standing interest in developing an effective vaccine (5-7).…”

Section: Gm-csf Transgene-based Adjuvant Allows the Establishment Of mentioning

confidence: 99%

GM-CSF Transgene-Based Adjuvant Allows the Establishment of Protective Mucosal Immunity Following Vaccination with Inactivated Chlamydia trachomatis

Xing

Brunham

2002

The Journal of Immunology

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Cellular and humoral immune responses induced following murine Chlamydia trachomatis infection confer almost sterile protection against homologous reinfection. On the other hand, immunization with inactivated organism induces little protective immunity in this model system. The underlying mechanism(s) that determines such divergent outcome remains unclear, but elucidating the mechanism will probably be important for chlamydial vaccine development. One of the distinct differences between the two forms of immunization is that chlamydia replication in epithelial cells causes the secretion of a variety of proinflammatory cytokines and chemokines, such as GM-CSF, that may mobilize and mature dendritic cells and thereby enhance the induction of protective immunity. Using a murine model of C. trachomatis mouse pneumonitis lung infection and intrapulmonary adenoviral GM-CSF transfection, we demonstrate that the expression of GM-CSF in the airway compartment significantly enhanced systemic Th1 cellular and local IgA immune responses following immunization with inactivated organisms. Importantly, immunized mice had significantly reduced growth of chlamydia and exhibited less severe pulmonary inflammation following challenge infection. The site of GM-CSF transfection proved important, since mice immunized with inactivated organisms after GM-CSF gene transfer by the i.p. route exhibited little protection against pulmonary challenge, although i.p. immunization generated significant levels of systemic Th1 immune responses. The obvious difference between i.p. and intrapulmonary immunization was the absence of lung IgA responses following i.p. vaccination. In aggregate, the findings demonstrate that the local cytokine environment is critical to the induction of protective immunity following chlamydial vaccination and that GM-CSF may be a useful adjuvant for a chlamydial vaccine.

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“…Chlamydia infection begins in the lower genital tracts; however, the diseases induced by chlamydia such as pelvic inflammatory disease (PID), infertility, and ectopic pregnancy take place in the fallopian tubes in the upper genital tracts [2,45,46]. Therefore, chlamydia must overcome host immunity, particularly in the genital mucosa that controls the spread and ascension of chlamydia.…”

Section: Discussionmentioning

confidence: 99%

“…Chlamydia trachomatis (C. trachomatis) infection in the lower genital tract (LGT) of women can lead to inflammatory pathologies such as hydrosalpinx in the upper genital tract (UGT), resulting in severe complications, including ectopic pregnancy and infertility [1][2][3]. More than 1.4 million cases of chlamydial infection are reported to the Centers for Disease Control and Prevention (CDC) in the United States annually [4], but the actual number of C. trachomatis infections is likely to be significantly higher since many infections are asymptomatic and remain undiagnosed.…”

Section: Introductionmentioning

confidence: 99%

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

Zhang

Zhong

Cai

et al. 2017

J Infect Dev Ctries

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Introduction: Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated. The pathological mechanisms of chlamydia-induced disease remain largely unknown, but it has been proposed that CPAF, a chlamydia-secreted serine protease, may play major roles in aiding chlamydial infection and contribute to chlamydia pathogenesis during in vivo infection. According to previous results, CPAF targets host immunity by degrading antimicrobial peptides and neutralizing complement activity; however, whether CPAF is involved in chlamydial antigen presentation has never been reported. Methodology: Antigen presentation assay was used to monitor the effects of CPAF on OT1-, OT2-, and chlamydia T cell antigen-mediated antigen presentation. In vitro cell-free degradation assay was used to detect CPAF processing of chlamydia T cell antigens. Results: We found that CPAF preferably inhibits OT2-but not OT1-mediated antigen presentation. CPAF inhibits OT2 antigen presentation by direct proteolytic cleavage in the wild type CPAF, but not enzymatic mutants. Importantly, several previously identified chlamydial T cell antigens were selectively degraded by CPAF when co-incubated in vitro. In addition, specific inhibition T cell antigen presentation by CPAF was correlated with T cell antigen cleavage by CPAF in vitro assay. Conclusions: Our experiments demonstrated that CPAF selectively and specifically degrades chlamydial T cell antigens, which chlamydia may utilize as a novel mechanism for evading host immune responses to promote chlamydia survival.

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Chlamydia trachomatis: Its Role in Tubal Infertility

Cited by 241 publications

References 18 publications

Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2

Identification by sequence analysis of two-site posttranslational processing of the cysteine-rich outer membrane protein 2 of Chlamydia trachomatis serovar L2

GM-CSF Transgene-Based Adjuvant Allows the Establishment of Protective Mucosal Immunity Following Vaccination with Inactivated Chlamydia trachomatis

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

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