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Sexual dimorphism in bacterial infections
Periodontal infections show sexual dimorphism, for instance, men are more susceptible than women to develop periodontitis, which as other infections are mainly attributed to the elevated production of pro-inflammatory cytokines in response to differential gene regulation through the action of sex steroid hormones. Interestingly, chronic periodontal inflammation is considered a cause of endothelial dysfunction by inducing reactive oxygen species production, that in turn contributes to the development of cardiovascular diseases, which are more frequent in men than in women.
Testosterone generally functions as a suppressor at early stages of infection, but as an activator during the late response to infection, as it occurs during sepsis; whereas, estradiol acts as an activator, and progesterone functions as an immunosuppressive agent, mainly during pregnancy.
In general, males are more susceptible to gastrointestinal and respiratory bacterial diseases and sepsis, while females are more susceptible to genitourinary tract bacterial infections. However, these incidences depend on the population evaluated, animal model and the bacterial species. Female protection against bacterial infections and the associated complications is assumed to be due to the pro-inflammatory effect of estradiol, while male susceptibility to those infections is associated with the testosterone-mediated immune suppression.
Certain gastrointestinal infections are more recurrent and severe in men than in women. This sexual dimorphism can be explained in part because of behavioral differences during hygiene and eating practices, such as handwashing before food handling and eating, storage, refrigeration, and defrosting practices, and tendency of men to eat undercooked or raw food, as well as to ingest roadside food .
During gastrointestinal injury, males produce predominantly pro-inflammatory cytokines, as compared with females whose intestine produce anti-inflammatory factors. in turn, the inflammatory response in males leads to perforation and cell necrosis at the site of infection.
Infections caused by Helicobacter pylori affect predominantly males, and its outcomes, such as gastritis, peptic ulcer, and gastric cancer, are also more frequent in males
It has been suggested that male sex is a frequent risk factor and a predictor of worse outcome for most of the respiratory tract infections, with exception of some upper respiratory tract infections (sinusitis, tonsillitis, and otitis externa) that are more frequently found in females.
The incidence of community-acquired pneumonia is higher in men than in women, and this incidence increases by age, especially in infections with Streptococcus pneumoniae, Streptococcus pyogenes, Chlamydophila pneumonia, and Legionella pneumophila.
In fact, male gender is considered as one of the four risk factors associated with the development of sepsis in general surgical and post-traumatic patients, with a hospital mortality rate of 70% in male and 26% in female patients.
One of the most used models to simulate bacteremia is LPS injection into bloodstream, which is known as experimental endotoxemia. Although there are controversies about the mechanisms involved in the sexual dimorphism of LPS response, it is accepted that males are more affected than females in LPS-induced endotoxemia.
A large number of genes related to immune functions are located on the X chromosome, X-linked mosaicism allows women to respond with a more expanded immune repertoire as compared with men.
Among other diseases that display a sex-based predominance are urinary tract infections (UTIs), which are present in females more often than in males. UTIs in women occur more frequently than in men due to anatomical and physiological differences; for example, the urethra is shorter than that of men, and the distance between the anus and urethral meatus is also shorter in women. Additionally, the perimeatal region has less humidity in men than in women and prostatic secretions show antibacterial activity; therefore, the probability of bacterial colonization and development of infection is lower in men.
Sexually transmitted infections also have female predominance; as it is the case of infections of the genital tract caused by Chlamydia and and Neisseria gonorrhoeae.
Aging and menopause also influence the immune system function, increasing the predisposition to infections. During menopause, there is a significant reduction in sex steroid hormone synthesis with a concomitant decrease in immune cell levels and their functional capacity.
