AUTHOR=Er-Lukowiak Marco , Hänzelmann Sonja , Rothe Moritz , Moamenpour David T. , Hausmann Fabian , Khatri Robin , Hansen Charlotte , Boldt Jennifer , Bärreiter Valentin A. , Honecker Barbara , Bea Annika , Groneberg Marie , Fehling Helena , Marggraff Claudia , Cadar Dániel , Bonn Stefan , Sellau Julie , Lotter Hanna TITLE=Testosterone affects type I/type II interferon response of neutrophils during hepatic amebiasis JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1279245 DOI=10.3389/fimmu.2023.1279245 ISSN=1664-3224 ABSTRACT=

Differences in immune response between men and women may influence the outcome of infectious diseases. Intestinal infection with Entamoeba histolytica leads to hepatic amebiasis, which is more common in males. Previously, we reported that innate immune cells contribute to liver damage in males in the murine model for hepatic amebiasis. Here, we focused on the influences of sex and androgens on neutrophils in particular. Infection associated with neutrophil accumulation in the liver was higher in male than in female mice and further increased after testosterone treatment in both sexes. Compared with female neutrophils, male neutrophils exhibit a more immature and less activated status, as evidenced by a lower proinflammatory N1-like phenotype and deconvolution, decreased gene expression of type I and type II interferon stimulated genes (ISGs) as well as downregulation of signaling pathways related to neutrophil activation. Neutrophils from females showed higher protein expression of the type I ISG viperin/RSAD2 during infection, which decreased by testosterone substitution. Moreover, ex vivo stimulation of human neutrophils revealed lower production of RSAD2 in neutrophils from men compared with women. These findings indicate that sex-specific effects on neutrophil physiology associated with maturation and type I IFN responsiveness might be important in the outcome of hepatic amebiasis.