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Testosterone overactivates the innate immune system
Hamburg, July 15th 2020 – 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, inter alia.
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 the 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".
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About the Bernhard Nocht Institute for Tropical Medicine
The Bernhard Nocht Institute for Tropical Medicine (BNITM) is Germany’s largest institution for research, treatment and training in the field of tropical diseases and new emerging infections. The current scientific focus is on malaria, haemorrhagic fever viruses, immunology, epidemiology and clinical studies of tropical infections as well as on the mechanisms of the viral transmission by mosquitoes. For the handling of highly pathogenic viruses and infected insects, the Institute has laboratories of the highest biosafety level (BSL-4) and a BSL-3 insectary. The Institute has been appointed by the Federal Ministry of Health as the National Reference Center (NRC) for the detection of all tropical pathogens as well as by the WHO as Collaborating Center for arboviruses and haemorrhagic fever viruses. In collaboration with the Ghanaian Health Ministry and the University of Kumasi the Institute has been operating a modern research and training center in the West-African rain forest for over ten years, which is also available to external research groups.
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). https://doi.org/10.1038/s41467-020-17260-y