Testosterone affects type I/type II interferon response of neutrophils during hepatic amebiasis

TY - JOUR

T1 - Testosterone affects type I/type II interferon response of neutrophils during hepatic amebiasis

AU - Er-Lukowiak, Marco

AU - Hänzelmann, Sonja

AU - Rothe, Moritz

AU - Moamenpour, David T

AU - Hausmann, Fabian

AU - Khatri, Robin

AU - Hansen, Charlotte

AU - Boldt, Jennifer

AU - Bärreiter, Valentin A

AU - Honecker, Barbara

AU - Bea, Annika

AU - Groneberg, Marie

AU - Fehling, Helena

AU - Marggraff, Claudia

AU - Cadar, Dániel

AU - Bonn, Stefan

AU - Sellau, Julie

AU - Lotter, Hanna

N1 - Copyright © 2023 Er-Lukowiak, Hänzelmann, Rothe, Moamenpour, Hausmann, Khatri, Hansen, Boldt, Bärreiter, Honecker, Bea, Groneberg, Fehling, Marggraff, Cadar, Bonn, Sellau and Lotter.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

KW - Humans

KW - Male

KW - Female

KW - Mice

KW - Animals

KW - Neutrophils

KW - Liver Abscess, Amebic

KW - Testosterone/pharmacology

KW - Interferon Type I

KW - Interferon-gamma

U2 - 10.3389/fimmu.2023.1279245

DO - 10.3389/fimmu.2023.1279245

M3 - SCORING: Journal article

C2 - 38179044

VL - 14

SP - 1279245

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -