The role of iron in the course of inflammation induced by uropathogenic E. coli (UPEC) infection in mouse epididymis and testis
2Institute of Anatomy and Cell Biology, Unit of Reproductive Biology, Justus-Liebig-University of Giessen, Germany
Iron is an essential nutrient for both hosts and pathogens, and they compete for iron during infection. Uropathogenic Escherichia coli (UPEC) is a gram-negative pathovar that expresses many iron acquisition systems to survive in a low-iron environment. UPEC infection of the male genito-urinary tract often results in long-term sperm-count reduction. The host immune imperative is to limit the availability of iron to the bacteria. Little is known regarding the mechanisms underlying this host-iron-UPEC interaction. The iron regulatory proteins, IRP1 and IRP2 determine cellular iron availability through post transcriptional modulation of iron-transport and -storage protein expression. Therefore, we hypothesize that iron availability influences host-pathogen interaction, which in turn, can modulate the course of UPEC mediated epididymo-orchitis.
To examine the hypothesis, we used mice with targeted deletions of the iron regulatory proteins (IRP)1 and 2, inducing a well-established bacterial epididymo-orchitis mouse model. After 7 days of infection, we analyzed the inflammation and iron homeostasis in testis and epididymis using histological, cellular, and molecular biology techniques. We observed an increase in neutrophil-infiltration in infected Irp2-/- mice compared to Wt mice, which correlated with higher transcript levels of Tnf-α, Il1β, Il10, and Lcn2 in the cauda and testis of these mice. In addition, infection dependent changes in the ferritin bound iron and subunit compositions were detected. Further, deletion of Irp1 showed a protective effect by reducing the inflammatory response to infection in the epididymis. The mechanism behind this protective action of Irp1 deletion is currently being investigated.