Role of Sex Steroid Hormones in Bacterial-Host Interactions

Figure 2

Effects of sex steroid hormones on bacterial infections. In general, male mammals are more susceptible to bacterial infections and its negative outcomes than their female counterparts. This is due to the suppressor effect of testosterone on the immune system, while estradiol acts as an activator of the immune system. Testosterone reduces the NK cell activity and induces the production of anti-inflammatory cytokines such as IL-10, whereas it reduces the production of proinflammatory cytokines such as TNFα through the inhibition of NFκB. This conduces to an inappropriate proinflammatory response that in turn allows the progression of the infection and its negative effects, such as an increase in mortality. In some cases, the limited proinflammatory response leads to a latent infection that can be abated and conduces to recovery. Progesterone acts as a modulator of the immune system due to its suppressing effects by reducing the NK cell activity, inducing the production of IL-4, IL-5 and IL-10 and increasing the expression of SOCS1, while inhibiting the production of IFNγ and TNFα, which avoid the development of bacterial infections, subsequent bacteremia, and sepsis. However, in high levels, for example during pregnancy, progesterone predisposes to some bacterial infections due to reduced proinflammatory responses. On the other hand, estradiol enhances the NK cell activity, and through the activation of NFκB, induces the production TNFα, IL-1, IL-6. IL-17, and IL-23, while inhibiting the production of IL-4, IL-10, IL-12, and TGF-β, and allows the bacterial clearance and recovery from infection. However, estradiol can also produce an excessive proinflammatory response and increased mortality as a consequence of susceptibility to infection and multiple organ failure. +, increase; −, reduction.