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

  • Marco Er-Lukowiak (Shared first author)
  • Sonja Hänzelmann (Shared first author)
  • Moritz Rothe
  • David T Moamenpour
  • Fabian Hausmann
  • Robin Khatri
  • Charlotte Hansen
  • Jennifer Boldt
  • Valentin A Bärreiter
  • Barbara Honecker
  • Annika Bea
  • Marie Groneberg
  • Helena Fehling
  • Claudia Marggraff
  • Dániel Cadar
  • Stefan Bonn
  • Julie Sellau (Shared last author)
  • Hanna Lotter (Shared last author)

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.

Bibliographical data

Original languageEnglish
ISSN1664-3224
DOIs
Publication statusPublished - 12.2023

Comment Deanary

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

PubMed 38179044