Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Sellau J,Groneberg M,Fehling H,Thye T,Hoenow S,Marggraff C,Weskamm M,Hansen C,Stanelle-Bertram S,Kuehl S,Noll J,Wolf V,Metwally NG,Hagen SH,Dorn C,Wernecke J,Ittrich H,Tannich E,Jacobs T,Bruchhaus I,Altfeld M,Lo

doi

10.1038/s41467-020-17260-y

subject

Has Abstract

pub_date

2020-07-10 00:00:00

pages

3459

issue

1

issn

2041-1723

pii

10.1038/s41467-020-17260-y

journal_volume

11

pub_type

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