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, Marie 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 and Hannelore Lotter ()
Additional contact information
Julie Sellau: Bernhard Nocht Institute for Tropical Medicine
Marie Groneberg: Bernhard Nocht Institute for Tropical Medicine
Helena Fehling: Bernhard Nocht Institute for Tropical Medicine
Thorsten Thye: Bernhard Nocht Institute for Tropical Medicine
Stefan Hoenow: Bernhard Nocht Institute for Tropical Medicine
Claudia Marggraff: Bernhard Nocht Institute for Tropical Medicine
Marie Weskamm: Bernhard Nocht Institute for Tropical Medicine
Charlotte Hansen: Bernhard Nocht Institute for Tropical Medicine
Stephanie Stanelle-Bertram: Leibniz Institute for Experimental Virology
Svenja Kuehl: Bernhard Nocht Institute for Tropical Medicine
Jill Noll: Bernhard Nocht Institute for Tropical Medicine
Vincent Wolf: Bernhard Nocht Institute for Tropical Medicine
Nahla Galal Metwally: Bernhard Nocht Institute for Tropical Medicine
Sven Hendrik Hagen: Heinrich Pette Institute
Christoph Dorn: Amedes Experts
Julia Wernecke: University Medical Center Hamburg-Eppendorf
Harald Ittrich: University Medical Center Hamburg-Eppendorf
Egbert Tannich: Bernhard Nocht Institute for Tropical Medicine
Thomas Jacobs: Bernhard Nocht Institute for Tropical Medicine
Iris Bruchhaus: Bernhard Nocht Institute for Tropical Medicine
Marcus Altfeld: Heinrich Pette Institute
Hannelore Lotter: Bernhard Nocht Institute for Tropical Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17260-y

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