Epidermal Growth Factor Receptor and Transforming Growth Factor β Signaling Pathways Cooperate To Mediate Pathogenesis.

Human genital infection is a major public health concern due to the serious reproductive system complications. binds several receptor tyrosine kinases (RTKs) on host cells, including the epidermal growth factor receptor (EGFR), and activates cellular signaling cascades for host invasion, cytoskeletal remodeling, optimal inclusion development, and induction of pathogenic epithelial-mesenchyme transition (EMT). also upregulates transforming growth factor beta (TGF-β) expression, whose signaling pathway synergizes with the EGFR cascade, but its role in infectivity, inclusions, and EMT induction is unknown.

Evaluation of a Single Dose of Azithromycin for Trachoma in Low-Prevalence Communities.

Purpose: Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is the leading infectious cause of blindness worldwide and is targeted for elimination as a public health problem. We sought to determine whether a one-time azithromycin mass treatment would reduce trachomatous inflammation-follicular (TF) levels below the elimination threshold of 5% in communities with disease prevalence between 5 and 9.9%.

The molecular mechanism of induction of unfolded protein response by Chlamydia.

The unfolded protein response (UPR) contributes to chlamydial pathogenesis, as a source of lipids and ATP during replication, and for establishing the initial anti-apoptotic state of host cell that ensures successful inclusion development. The molecular mechanism(s) of UPR induction by Chlamydia is unknown. Chlamydia use type III secretion system (T3SS) effector proteins (e.

Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis.

The reproductive system complications of genital chlamydial infection include fallopian tube fibrosis and tubal factor infertility. However, the molecular pathogenesis of these complications remains poorly understood. The induction of pathogenic epithelial-mesenchymal transition (EMT) through microRNA (miRNA) dysregulation was recently proposed as the pathogenic basis of chlamydial complications.

The Roles of Unfolded Protein Response Pathways in Chlamydia Pathogenesis.

Chlamydia is an obligate intracellular bacterium that relies on host cells for essential nutrients and adenosine triphosphate (ATP) for a productive infection. Although the unfolded protein response (UPR) plays a major role in certain microbial infectivity, its role in chlamydial pathogenesis is unknown. We hypothesized that Chlamydia induces UPR and exploits it to upregulate host cell uptake and metabolism of glucose, production of ATP, phospholipids, and other molecules required for its replicative development and host survival.

Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis.

Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated.

Development of PCR assays for detection of Trichomonas vaginalis in urine specimens.

Trichomonas vaginalis infections are usually asymptomatic or can result in nonspecific clinical symptoms, which makes laboratory-based detection of this protozoan parasite essential for diagnosis and treatment. We report the development of a battery of highly sensitive and specific PCR assays for detection of T. vaginalis in urine, a noninvasive specimen, and development of a protocol for differentiating among Trichomonas species that commonly infect humans.

Prevention of Chlamydia-induced infertility by inhibition of local caspase activity.

Tubal factor infertility (TFI) represents 36% of female infertility and genital infection by Chlamydia trachomatis (C. trachomatis) is a major cause. Although TFI is associated with host inflammatory responses to bacterial components, the molecular pathogenesis of Chlamydia-induced infertility remains poorly understood.

Distribution of Chlamydia trachomatis genovars among youths and adults in Brazil.

Despite a high prevalence of sexually transmitted Chlamydia trachomatis infections in Brazil and other countries in South America, very little is known about the distribution of C. trachomatis genovars. In this study, we genotyped C.

Role of T lymphocytes in the pathogenesis of Chlamydia disease.

Vaccines are needed to prevent the oculogenital diseases of Chlamydia trachomatis. Infected hosts develop immunity, although temporary, and experimental vaccines have yielded significant protective immunity in animal models, fueling the impetus for a vaccine. Because infections cause sequelae, the functional relationship between infection- and vaccine-induced immunity is unclear.

Evaluation of the rapid BioStar optical immunoassay for detection of Chlamydia trachomatis in adolescent women.

We evaluated the performance of the BioStar Chlamydia OIA (optical immunoassay) in adolescent females (n = 261) from an inner city population. With a reference standard of two different nucleic acid amplification tests, the sensitivity and specificity of the BioStar Chlamydia OIA were 59.4 and 98.

Involvement of LEK1 in dendritic cell regulation of T cell immunity against Chlamydia.

We investigated the hypothesis that the enhanced Ag-presenting function of IL-10-deficient dendritic cells (DCs) is related to specific immunoregulatory cytoskeletal molecules expressed when exposed to Ags. We analyzed the role of a prominent cytoskeletal protein, LEK1, in the immunoregulation of DC functions; specifically cytokine secretion, costimulatory molecule expression, and T cell activation against Chlamydia. Targeted knockdown of LEK1 expression using specific antisense oligonucleotides resulted in the rapid maturation of Chlamydia-exposed DCs as measured by FACS analysis of key activation markers (i.

Chlamydia trachomatis serovars among strains isolated from members of rural indigenous communities and urban populations in Australia.

We genotyped Chlamydia trachomatis strains from 45 women or men living in either a rural indigenous community or in urban heterosexual communities. We found six different C. trachomatis serovars: E (n = 22; 48.

The natural history of untreated Chlamydia trachomatis infection in the interval between screening and returning for treatment.

Background: Studies of the natural history of genital chlamydial infections in humans are sparse and have had study design limitations. An improved understanding of chlamydial natural history may influence recommendations for elements of control efforts such as chlamydia screening frequency or time parameters for partner notification.

Methods: Addressing limitations of prior studies in part, we are prospectively studying chlamydial natural history in sexually transmitted diseases clinic patients in the interval between screening and returning for treatment of positive chlamydial tests.

Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines.

Effective delivery systems are needed to design efficacious vaccines against the obligate intracellular bacterial pathogen, Chlamydia trachomatis. Potentially effective delivery vehicles should promote the induction of adequate levels of mucosal T-cell and antibody responses that mediate long-term protective immunity. Antigen targeting to the nasal-associated lymphoid tissue (NALT) is effective for inducing high levels of specific immune effectors in the genital mucosa, and therefore suitable for vaccine delivery against genital chlamydial infection.

Delivery of Chlamydia vaccines.

The plethora of ocular, genital and respiratory diseases of Chlamydia, including nongonococcal urethritis, cervicitis pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, conjunctivitis, blinding trachoma and interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult onset asthma and Alzheimer's disease, still pose a considerable public health challenge to many nations. Although antibiotics are effective against Chlamydia when effectively diagnosed, asymptomatic infections are rampart, making clinical presentation of complications often the first evidence of an infection. Consequently, the current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections.

Developing effective delivery systems for Chlamydia vaccines.

Members of the genus Chlamydia cause a plethora of ocular, genital and respiratory diseases, with severe complications, such as blinding trachoma, pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility, interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult-onset asthma and Alzheimer's disease. The current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections. There are three essential and mutually inclusive areas of challenge confronting researchers developing Chlamydia vaccines.