Genital Chlamydia trachomatis infection and infertility in Malaysia

Abstract

Background: Genital Chlamydia trachomatis infection can cause pelvic inflammatory disease and infertility in female by damaging cervical columnar epithelial cells. Recent reports have shown increased cases of newly reported chlamydial infection worldwide. However, at present, there is no effective vaccine available for the prevention of genital chlamydial infection. Insights into the host response of the human cervical epithelial cells against C. trachomatis infection are crucial to design a better prevention and vaccination strategy. Methods and materials: Here, we examined the prevalence of the C. trachomatis infection and the association with women's health in Malaysia. To investigate the influence of the C. trachomatis infection on human epithelial cells, we applied isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique and liquid chromatography-tandem mass spectrometry (LC-MS3) analysis for elucidation of host proteome changes in the C. trachomatis-infected HeLa-229 human cervical epithelial cells. In addition, cytokine response following stimulation with multiple C. trachomatis antigens (CPAF, HSP60 and MOMP) were also examined. Results: Here, we reported that the prevalence of genital chlamydial infection among the ostetrics and gynecology patients was alarmingly high at 51.1% (92/180). Our data also showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). Our proteomic work discovered a significant array of host proteins which participated in the early C. trachomatis infection. We highlighted involvement of eukaryotic initiation factor 2 (eIF2), mammalian target of rapamycin (mTOR), ubiquitination, clathrin-mediated endocytosis, tRNA charging and glycolysis signaling pathways in the host cells to eradicate the bacteria invasion. The bacteria infection was also associates with other complications such as increased inflammation and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Conclusion: Our study describes a high prevalence of C. trachomatis among Malaysian O&G patients and highlights distinct ability of C. trachomatis in manipulating host proteins and triggering pro-inflammatory response.