Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA

Abstract

Malaria is the most lethal parasitic disease worldwide; men exhibit higher mortality and more severe symptomatology than women; however, in most studies of immune response in malaria, sex is not considered a variable. Sex hormones 17β-oestradiol and testosterone are responsible for the main physiological differences between sexes. When interacting with their receptors on different immune cells, they modify the expression of genes that modulate cell proliferation, differentiation, and synthesis of cytokines. The immunosuppressive activity of testosterone is well accepted; however, its participation in the sexual dimorphism of the immune response to malaria has not been studied. In this work, we analysed whether altering the concentration of testosterone, through increasing the concentration of this hormone for exogenous administration for three weeks, or gonadectomy before infection with Plasmodium berghei ANKA affects different cells of the immune response necessary for parasite clearance. We also assessed the concentration of pro-and anti-inflammatory cytokines in male and female CBA/Ca mice infected or not with the parasite. Our results show that testosterone changes affect females more than males, resulting in sex-associated patterns. Testosterone administration increased parasitaemia in intact males while reducing it in intact females leading to a dimorphic pattern. In addition, gonadectomy increased parasitaemia in both sexes. Moreover, testosterone administration prevented both weight loss caused by the infection in females and hypothermia in gonadectomized mice of both sexes. Boosting testosterone concentration increased CD3+ and CD8+ populations but decreased the B220+ cells exclusively in females. Additionally, testosterone reduced IFN-γ concentration and increased IL-6 levels only in females, while in males, testosterone increased the number of NK cells. Finally, gonadectomy decreased TNF-α concentration in both sexes. Our results demonstrate that testosterone induces different patterns depending on sex and testosterone concentration. The results of this work contribute to understanding the impact of modifying testosterone concentration on the immune response specific against Plasmodium and the participation of this hormone in sexual dimorphism in malaria.

Immune regulation based on sex differences in ischemic stroke pathology

“…Testosterone and dihydrotestosterone, two types of androgens, modulate the immune system by favoring the development of a Th1 response and activating CD8 + T cells while enhancing the NK cell response, elevating TNF-α, and decreasing IL-10 ( 49 – 51 ). When testosterone is present in vitro , the ratio of Th1:Th2 cells in male peripheral blood shifts toward more Th1 cells ( 52 ).…”

DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA

“…However, gonadectomy decreased the temperature in the uninfected groups in both sexes. It is possible that this surgery, by decreasing the concentration of 17β-estradiol [ 7 ], deregulated thermogenesis in adipose tissue [ 36 ]. In addition, DHEA increases mitochondrial FADH 2 synthesis, resulting in heat generation [ 37 ].…”

“…Quantification of cell populations was performed by flow cytometry as previously described [ 7 ]. Briefly, on day 8 post infection, mice were sacrificed, the spleen was disaggregated on nylon mesh, cells were washed with PBS and erythrocytes were removed with a lysis solution (Beckton and Dickinson, Franklin Lakes, NJ, USA).…”

“…Although this sexual condition is accepted, few articles have analyzed this phenomenon in both sexes [ 4 ]. 17β-estradiol and testosterone are involved in the sexual dimorphism that occurs in the immune response in malaria [ 5 , 6 , 7 ]. Both hormones modify survival and cellular and humoral immune responses in Plasmodium infections [ 2 , 8 , 9 ].…”

Вплив Тестостерону На Запальні Процеси (Огляд Літератури)

“…У даній роботі була зібрана інформація про прямі і непрямі механізми і наслідки впливу тестостерону на продукцію прозапальних і протизапальних медіаторів. Автори[12,13,14, 15, 16,17,18, 19] показують, що тестостерон знижує активність запальних процесів, за рахунок негативного впливу на жирову тканину та інгібування синтезу прозапальних цитокінів напряму. А також було частково розглянуто його вплив на метаболічні процеси і його кореляцію з ІМТ.…”