Higher expression of ferritin protects Chlamydia trachomatis infected HeLa 229 cells from reactive oxygen species mediated cell death

Apoptosis plays an important role in modulating the pathogenesis of a variety of infectious diseases. Chlamydial infection protects cells against different forms of apoptosis: extrinsic, intrinsic, and granzyme B mediated. Redox reactions are central to the life and death decision of cells and pathogens and an intimate relationship exists between oxidative stress and iron metabolism. The link between redox status and ferritin was largely unexplored in chlamydia-infected cells. In the present study, we showed that Chlamydia trachomatis (CT) infection induced FHC protein in HeLa cells. FHC induction by CT-infected cells stably expressing FHC blunted ROS production compared with mock infected cells, and the infected cells were relatively resistant to apoptosis induced by [H.sub.2][O.sub.2]. We also demonstrated that endogenous FHC overexpression correlates well with the stabilization of the mitochondrial membrane potential in CT-infected cells. Increased expression of FHC is independent of iron supplementation (FAC) and depletion (DFO) in CT-infected cells. These data suggest that FHC up-regulation is an acute response of HeLa cells against CT infection and that FHC exerts anti-apoptotic activity against oxidative stress. Key words: Chlamydia trachomatis, ferritin, reactive oxygen species, apoptosis, mitochondrial membrane potential. L'apoptose joue un role important dans la modulation de la pathogenese d'une variete de maladies infectieuses. L'infection par la chlamydia protege les cellules contre differentes formes d'apoptose : extrinseque, intrinseque et dependante de la granzyme B. Les reactions d'oxydoreduction sont centrales au cheminement vers la survie ou la mort des cellules et des pathogenes, et il existe un lien etroit entre le stress et le metabolisme du fer. Le lien entre le statut d'oxydoreduction et la ferritine a ete largement negligee chez les cellules infectees par la chlamydia. Dans cette etude, nous avons montre; qu'une infection par Chlamydia trachomatis (CT) induisait la proteine FHC chez les cellules HeLa. L'induction de FHC chez les cellules infectees par CT et exprimant la FHC de facjon stable interrompait la production d'ERO comparativement aux cellules infectees a blanc, et ces cellules eetaient relativement resistantes a l'apoptose induite par le [H.sub.2][O.sub.2]. Nous avons aussi demontree que la surexpression de FHC endogene etait bien relieeea la stabilisation du potentiel membranaire mitochondrial chez les cellules infectees par CT. L'augmentation de l'expression de FHC est independante de la supplementation ou de la depletion en fer chez les cellules infectees par CT. Ces resultats suggerent que la stimulation de l'expression de FHC constitue une reponse aigue des cellules HeLa contre l'infection par CT, et que la FHC exerce une activite anti-apoptotique lors d'un stress oxydant. Mots-cles : Chlamydia trachomatis, ferritine, espeeces reactives d'oxygene, apoptose, potentiel membranaire mitochondrial. [Traduit par la Redaction]
Introduction Apoptosis, or programmed cell death, is an evolutionary conserved, strictly regulated, genetic and biochemical program that plays critical roles during development and tissue homeostasis in multicellular organisms (Zakeri and [...]