Sex Hormones and Immune Response: Unveiling the Link to Morbidity and Mortality
Infectious diseases affect individuals differently based on their sex, with men often facing higher morbidity and mortality rates. Numerous studies have identified differences in the immune system as a potential reason for this sex bias. Researchers have found that sex hormones – estrogen, progesterone, and testosterone – play a vital role in shaping the immune response at various levels.
Women of reproductive age, who have higher estrogen levels, have been observed to exhibit stronger proinflammatory responses to inflammatory stimuli compared to men and post-menopausal women. While this may lead to a more active pathogen response, it could also result in detrimental immunopathology to infections or the development of autoimmune reactions.
A recent thesis aimed to investigate the contribution of sex hormones and sex hormone receptors (SHR) to sex differences in immune response. The focus was on studying peripheral blood mononuclear cells (PBMCs) in healthy individuals and those with asymptomatic Torque Teno Virus (TTV) infection, as well as individuals with acute Puumala virus infection.
In one study, researchers examined the expression of SHR and immune response genes in PBMCs from healthy premenopausal (pre-MP) women throughout the menstrual cycle. The expression levels were measured using a qPCR Array. While SHR expression remained relatively stable during the cycle, several key immune regulatory genes showed significant expression during the ovulatory and mid luteal phases. Additionally, the study analyzed the expression of estrogen receptors (ERs) in different subsets of PBMCs. Surprisingly, they discovered that the isoform ERβ2 was more abundant than the wildtype ERβ1. These findings provide new insights into the influence of the menstrual cycle on the immune response.
Another study focused on using Torque Teno Virus as a secondary functional immune marker in men and women. The researchers estimated the expression of viral TTV DNA in PBMCs and analyzed it in relation to serum sex hormone levels. The results revealed that 50% of men, 25% of post-menopausal women, and 18% of premenopausal women tested positive for TTV. Interestingly, all TTV-positive premenopausal women exhibited hormonal aberrances and had lower progesterone levels compared to TTV-negative premenopausal women. This suggests that hormonal imbalances increase the prevalence of TTV, particularly in premenopausal women.
In a third study, researchers investigated the expression of estrogen receptors in PBMCs from patients with Nephropathia epidemica, a viral zoonotic disease caused by Puumala virus. This virus is known to affect more men than women. The expression of estrogen receptors in PBMCs and clinical laboratory results during the acute and convalescent phases were analyzed. The findings demonstrated differences in estrogen receptor expression, supporting previous observations that men and women present a different clinical picture when infected with Puumala virus.
Overall, this thesis sheds light on distinct patterns of immune response associated with sex hormone levels, SHR expression, and different phases of the menstrual cycle. It highlights the link between sex hormone levels and immune responses. Additionally, the discovery of the abundant ERβ2 isoform in PBMCs provides valuable new knowledge. Understanding these sex differences in immune response is crucial for optimizing healthcare and treatment strategies, as it may help explain the disparities in morbidity and mortality observed between men and women in infectious diseases.
