Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium
| Autor: | Xi-Yuan Wang, Wen-Liang Zhou, Lei Chen, Shen-Jiao Lu, Hao-Li Zhang, Jian-Bang Xu, Xiao-Fan Wei, Yi-Lin Zhang, Yun-Xin Zhu, Shuming He, Zhao-Rong Lun, Zhuo-Er Qiu, Li-Jiao Ke |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Prostaglandin RC955-962 Cystic Fibrosis Transmembrane Conductance Regulator medicine.disease_cause Physical Chemistry Biochemistry Epithelium Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Medical Conditions Animal Cells Arctic medicine. Tropical medicine Cyclic AMP Medicine and Health Sciences Chloride-Bicarbonate Antiporters Lipid Hormones Prostaglandin E2 Cells Cultured 030219 obstetrics & reproductive medicine Trichomoniasis biology Chemistry Eukaryota Protists Cystic fibrosis transmembrane conductance regulator medicine.anatomical_structure Infectious Diseases Vagina Physical Sciences Trichomonas Female Public aspects of medicine RA1-1270 Cellular Types Anatomy Trichomonas Vaginitis medicine.drug Research Article Anions Sexually Transmitted Diseases Dinoprostone Cell Line Andrology 03 medical and health sciences Chlorides medicine Trichomonas vaginalis Animals Humans Secretion Ions Public Health Environmental and Occupational Health Organisms Biology and Life Sciences Biological Transport Epithelial Cells Cell Biology Apical membrane medicine.disease Hormones Sperm Rats 030104 developmental biology Biological Tissue Germ Cells biology.protein Physiological Processes |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 15, Iss 4, p e0009319 (2021) |
| ISSN: | 1935-2735 |
| Popis: | Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl− and HCO3−. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl− and HCO3− secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl− transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl− signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment. Author summary Trichomonas vaginalis is a common sexually transmitted parasite that colonized the urogenital mucosa and causes trichomoniasis, a neglected sexually transmitted infection associated with multiple adverse reproductive outcomes in humans. However, the underlying mechanisms remain largely unknown. The epithelial cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel conducting both Cl− and HCO3−, which participates in the regulation of luminal fluid microenvironment conducive to the success of reproductive events. Prostaglandin E2 (PGE2), a bioactive molecule abundant in human seminal fluid, has been demonstrated to exhibit a robust pro-secretory action by activating CFTR in the female genital tract epithelial cells such as endometrial epithelium. These discoveries motivated the authors to investigate the effect of T. vaginalis infection on exogenous PGE2-induced transepithelial transport of electrolytes in vagina. Here, we found that in rat vaginal epithelium, luminal administration of PGE2 elicited a response of Cl− and HCO3− secretion mediated by cAMP-activated CFTR. However, T. vaginalis infection impaired transepithelial anion transport evoked by PGE2, which is probably related to the defective expression and function of CFTR. These outcomes may complement and expand our knowledge of the complex interaction between T. vaginalis and the infected host, providing a novel therapeutic strategy for disequilibrium in vaginal fluid microenvironment and infertility induced by T. vaginalis infection. |
| Databáze: | OpenAIRE |
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