Male sex affects type I/type II interferon response of neutrophils during hepatic Amebiasis
Hepatic amebiasis, a serious complication caused by the parasite Entamoeba histolytica, predominantly affects men. Earlier research in the murine disease model indicated that testosterone modulates an intense immune reaction, triggering destructive immunopathological changes in the liver. Inflammatory monocytes expressing proinflammatory chemokines, crucial for neutrophil recruitment, worsen this process. This study examines sex-related variances in neutrophils during hepatic amebiasis in a mouse model. Male subjects exhibited higher levels and recruitment of neutrophils compared to females. Androgens directly contributed to this bias, enhancing neutrophil recruitment and retarding maturation in response to infection. Transcriptomic analysis revealed diminished type I and II interferon-stimulated gene expression and reduced activation pathways in male neutrophils versus female neutrophils. Upon ex-vivo stimulation, female human neutrophils showed higher expression of a key type I interferon-stimulated gene (viperin/RSAD2) at the protein level, which was similar in mice after infection, and suppressed by testosterone. In male mice with hepatic amebiasis, sex-dependent factors led to recruitment of less active neutrophils, intensifying immunopathological damage to liver tissue. This sex disparity and testosterone's impact on interferon-stimulated genes hold implications beyond hepatic amebiasis, potentially influencing broader areas, including viral infectious diseases Overall design: Bone marrow and blood neutrophils from male and female Entamoeba histolytica infected mice and controls.