Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1
Julie Sellau, Marie Groneberg, Helena Fehling, Thorsten Thye, Stefan Hoenow, Claudia Marggraff, Leonie M. Weskamm, Charlotte Hansen, Stephanie Stanelle‐Bertram, Svenja Kuehl, Jill Noll, Vincent Wolf, Nahla Galal Metwally, Sven Hendrik Hagen, Christoph Dorn, Julia Wernecke, Harald Ittrich, Egbert Tannich, Thomas Jacobs, Iris Bruchhaus, Marcus Altfeld, Hannelore Lotter
Abstract
Hepatic amebiasis, predominantly occurring in men, is a focal destruction of the liver due to the invading protozoan Entamoeba histolytica. Classical monocytes as well as testosterone are identified to have important functions for the development of hepatic amebiasis in mice, but a link between testosterone and monocytes has not been identified. Here we show that testosterone treatment induces proinflammatory responses in human and mouse classical monocytes. When treated with 5α-dihydrotestosterone, a strong androgen receptor ligand, human classical monocytes increase CXCL1 production in the presence of Entamoeba histolytica antigens. Moreover, plasma testosterone levels of individuals undergoing transgender procedure correlate positively with the TNF and CXCL1 secretion from their cultured peripheral blood mononuclear cells following lipopolysaccharide stimulation. Finally, testosterone substitution of castrated male mice increases the frequency of TNF/CXCL1-producing classical monocytes during hepatic amebiasis, supporting the hypothesis that the effects of androgens may contribute to an increased risk of developing monocyte-mediated pathologies.