Male hormones promote excessive immune reaction

Wednesday, 15. July 2020

Hamburg. Sex hormones influence a certain group of immune cells to different extents. This was discovered by a research team from the Bernhard Nocht Institute for Tropical Medicine. The research group led by Hanna Lotter and Julie Sellau showed for the first time that monocytes, which are important for the immune response against invading parasites, are directly influenced by male sex hormones. This discovery was recently published in the journal Nature Communications. The work was done in cooperation with the group of Prof. Dr. Marcus Altfeld of the Heinrich Pette Institute, Leibniz Institute for Experimental Virology (HPI) with the support of the Landesforschungsförderung Hamburg.

Women and men differ in the frequency of certain diseases. Previous studies have shown that men are more susceptible to infectious diseases. Whereas women are more prone to chronic inflammation and autoimmune diseases. Apparently, sex-specific influences such as genetic factors or sex hormones affect the immune system.

In particular, infections with the monocellular parasite Entamoeba (E.) histolytica lead much more frequently to dangerous disease progressions in men such as amoebic liver abscesses. Using a mouse model, Hanna Lotter's team was able to clarify the underlying immune mechanisms. According to the researchers, testosterone is the driving force behind an overreaction of the innate immune system: It causes monocytes, which are actually supposed to protect against invading pathogens, to intensify certain inflammatory reactions in the liver and thus contribute significantly to liver damage.

In detail, it was shown that monocytes under the influence of testosterone increase the secretion of certain messenger substances. These messenger substances lead to the destruction of liver tissue and attract further immune cells to the site of infection. This further accelerates the damaging effect - a vicious circle.

Not only in mice but also in humans, the researchers found that monocytes produce increased amounts of such messenger substances under the influence of testosterone. They also found the effect in women who underwent testosterone therapy as part of a gender reassignment process.

The researcher Julie Sellau: "I am very pleased that this work has enabled us to clarify in detail the influence of male sex hormones on certain innate immune cells. This helps us to better understand sex-specific diseases and opens up new possibilities for targeted, personalized treatment approaches".


Original publication

Sellau, J. et al. Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1. Nature Communications 11, 3459 (2020).


This press release was originally published on the website of the Bernhard Nocht Institute for Tropical Medicine.