30th Annual Meeting of the German Society for Parasitology

Prof. Dr.

Gender inequity in the development of filarial lymphedema

Talk

Sex difference in hepatic amebiasis

Abstract text Infections with the protozoan parasite Entamoeba (E.) histolytica can lead to hepatic amebiasis, a severe, focal liver injury that is more common in men than in women. In the first and second funding period, we investigated immune mechanisms underlying liver damage and regeneration during intrahepatic parasitic infection the murine model for the disease. In summary, we found that initiation of the IL-23/IL-17 immunopathological axis leads to massive recruitment of classical, pro-inflammatory Ly6Chi monocytes through induction of C-C chemokine ligand 2 (CCL2). Liver destruction was finally mediated by TNFa produced by monocytes as well as liver resident macrophages. On the other hand, regeneration was promoted by anti-inflammatory, IL13+Arg1+ Ly6Clo monocytes. In the last funding period, we questioned whether i) sex hormones modulate the immunopathological functions of pro-inflammatory monocytes in the murine model for the disease and whether this is transferable to their human correlates, ii) which role plays the Hypoxia-inducible factor-1 alpha (HIF-1a) in balancing liver damage in male and female individuals and iii) what are the characteristics for immunopathological and protective monocytes. Hepatic amebiasis occurs with a clear sex bias towards male individuals. We have previously shown, that testosterone was found to have important functions for the development of hepatic amebiasis in mice, but a link between testosterone and monocytes has not been identified so far. In vivo as well as in vitro studies now revealed, that testosterone treatment triggers proinflammatory responses in human and murine classical monocytes. Testosterone substitution of castrated male mice increases the frequency of TNFa, CCL2 and CXCL1-producing classical monocytes during hepatic amebiasis, the latter cytokine further amplifies the recruitment of Ly6Chi monocytes but also that of neutrophils, which also contribute to tissue damage in hepatic amebiasis. Furthermore, androgen treatment of isolated human monocytes but also of individuals, undergoing gender reassignment, increased the production of these cytokines, supporting the hypothesis that androgens may contribute to an increased risk of developing monocyte-mediated pathologies.

Session VI
Sex and Gender in Parasitology

Appointment

Chairs

Programme

Session VISex and Gender in Parasitology

Appointment

Chairs

Programme

Session VI
Sex and Gender in Parasitology