Tail-specific protease is an essential virulence factor that mediates the differentiation of elementary bodies into reticulate bodies.

Tail-specific proteases (Tsp) are members of a widely distributed family of serine proteases that commonly target and process periplasmic proteins in Gram-negative bacteria. The obligately intracellular, Gram-negative encode a highly conserved Tsp homolog whose target and function are unclear. We identified a mutant with a nonsense mutation in .

A Genital Infection-Attenuated Chlamydia muridarum Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge.

spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors.

Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors.

Some members of the genus , including the human pathogen , infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the plasticity zone were not critical for murine genital tract infection.

Neutrophils Are Central to Antibody-Mediated Protection against Genital Chlamydia.

Determining the effector populations involved in humoral protection against genital chlamydia infection is crucial to development of an effective chlamydial vaccine. Antibody has been implicated in protection studies in multiple animal models, and we previously showed that the passive transfer of immune serum alone does not confer immunity in the mouse. Using the model of genital infection, we demonstrate a protective role for both -specific immunoglobulin G (IgG) and polymorphonuclear neutrophils and show the importance of an antibody/effector cell interaction in mediating humoral immunity.

Immunoglobulin-Based Investigation of Spontaneous Resolution of Chlamydia trachomatis Infection.

Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA) was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived response) and immunoglobulin G3 (IgG3; short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. Of these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia resolution.

IFNγ is Required for Optimal Antibody-Mediated Immunity against Genital Chlamydia Infection.

Defining the mechanisms of immunity conferred by the combination of antibody and CD4 T cells is fundamental to designing an efficacious chlamydial vaccine. Using the Chlamydia muridarum genital infection model of mice, which replicates many features of human C. trachomatis infection and avoids the characteristic low virulence of C.

Immunoglobulin-specific responses to Chlamydia elementary bodies in individuals with and at risk for genital chlamydial infection.

Renewed interest in chlamydia vaccination has revealed the need for a greater understanding of the seroprevalence of chlamydial infection in US populations. We used a Chlamydia trachomatis elementary body (EB)-based enzyme-linked immunosorbent assay to define the characteristics of the humoral immune response and to determine seroprevalence. Two groups were analyzed: one consisting of patients with current, laboratory confirmed, genital chlamydial infection (n = 98) and one group of individuals whose chlamydia infection history was unknown (n = 367).

Murine Chlamydia trachomatis genital infection is unaltered by depletion of CD4+ T cells and diminished adaptive immunity.

Chlamydia muridarum and Chlamydia trachomatis mouse models of genital infection have been used to study chlamydial immunity and vaccine development. To assess the protective role of CD4(+) T cells in resolving C. trachomatis and C.

Vaccination against Chlamydia genital infection utilizing the murine C. muridarum model.

Chlamydia trachomatis genital infection is a worldwide public health problem, and considerable effort has been expended on developing an efficacious vaccine. The murine model of C. muridarum genital infection has been extremely useful for identification of protective immune responses and in vaccine development.

CD4+ T cells and antibody are required for optimal major outer membrane protein vaccine-induced immunity to Chlamydia muridarum genital infection.

Despite effective antimicrobial chemotherapy, control of Chlamydia trachomatis urogenital infection will likely require a vaccine. We have assessed the protective effect of an outer membrane protein-based vaccine by using a murine model of chlamydial genital infection. Female mice were first vaccinated with Chlamydia muridarum major outer membrane protein (MOMP) plus the adjuvants CpG-1826 and Montanide ISA 720; then they were challenged with C.

A predominant role for antibody in acquired immunity to chlamydial genital tract reinfection.

Acquired immunity to murine Chlamydia trachomatis genital tract reinfection has long been assumed to be solely dependent on cell-mediated immunity. However, in this study, we identify a previously unrecognized protective role for Ab. Immunity develops in Ab-deficient mice following the resolution of primary chlamydial genital infection.

The protective effect of antibody in immunity to murine chlamydial genital tract reinfection is independent of immunoglobulin A.

The resolution of primary and secondary chlamydial genital infection in immunoglobulin A (IgA)-deficient (IgA(-/-)) mice was not different from that in IgA(+/+) mice. Furthermore, depletion of either CD4(+) or CD8(+) T cells prior to reinfection of IgA(+/+) or (-/-) mice had limited impact on immunity to reinfection. Thus, although antibody contributes importantly to immunity to chlamydial genital tract reinfection, IgA antibodies are not an absolute requirement of that protective response.

New insights into a persistent problem -- chlamydial infections.

Tissue tropism of clinical ocular and genital Chlamydia trachomatis strains is shown to be linked to the tryptophan synthase genotype. It is suggested that, in the presence of IFN-gamma, which depletes available tryptophan, there exist unique host-parasite interactions that may contribute to persistent chlamydial infection.

Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in atherosclerosis.

Objective: Growing evidence suggests that immune reactions to heat shock protein 60 (HSP60) are involved in atherogenesis. Because of the high phylogenetic conservation between microbial and human HSP60, bacterial infections might be responsible for breaking the tolerance to self-HSP60, which is expressed on the surface of stressed arterial endothelial cells.

Methods And Results: We purified serum antibodies to Escherichia coli HSP60 (GroEL), the 60-kD chlamydial HSP, and HSP65 of Mycobacterium tuberculosis by affinity chromatography from clinically healthy subjects with sonographically proven carotid atherosclerosis.

Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway.

Active inflammation and NF-kappaB activation contribute fundamentally to atherogenesis and plaque disruption. Accumulating evidence has implicated specific infectious agents including Chlamydia pneumoniae in the progression of atherogenesis. Chlamydial heat shock protein 60 (cHSP60) has been implicated in the induction of deleterious immune responses in human chlamydial infections and has been found to colocalize with infiltrating macrophages in atheroma lesions.