Role of Iron in Pathogenesis of Chlamydia trachomatis Infection in vitro

Abstract

Chlamydia trachomatis (CT) is a gram-negative obligate intracellular parasite responsible for newlinemyriad of diseases including trachoma, pelvic inflammatory diseases and infertility. newlineChlamydial biphasic developmental cycle is closely interwoven with host metabolic and newlineregulatory pathways for its requirements. Virtually all cells and organisms utilize iron as a newlinecofactor in a multitude of biochemical activities. Iron, as an essential nutrient and potential newlinetoxin poses an exquisite regulatory problem in biology and medicine. Availability of iron newlinedetermines the course and disease outcome of chlamydial infection. In the present study CThost newlineinteraction was assessed in HeLa 229 cells under iron depleted and supplemented newlineconditions. newlineIt was observed that at critical concentration of 25-50uM deferoxamine (DFO), CT infection newlinelead to greater sustenance of cells and delayed chlamydial developmental cycle as observed newlinein cell viability assay and direct fluorescence assays. Further irrespective of iron depletion newlineand supplementation CT infected HeLa cells showed decrease in surface expression of newlinetransferrin receptor (TfR) (flow cytometry), however level of ferritin heavy chain (FHC) newlineincreased as observed in immunoblotting. Intracellular ROS and mitochondrial membrane newlinepotential was analysed using DCFH-DA and JC-1 probes respectively. Level of ROS was newlinedampened, moreover mitochondrial membrane potential remained stable in iron depleted and newlinesupplemented conditions in CT infected cells. Increase in level of anti-apoptotic Bcl-2, Trx, newlinePPAR-and#947; and decrease in pro-apoptotic cytoplasmic cytochrome c , active caspase-3/8/9 and newlineBax was observed in CT infected cells. These results suggested that critical concentration newline(25-50uM) of DFO was synergistic to anti-apoptotic effect of CT.