Sex Steroids Mediate Bidirectional Interactions Between Hosts and Microbes

Abstract

The outcome of microbial infections in mammals, including humans, is affected by the age, sex, and reproductive status of the host suggesting a role for sex steroid hormones. Testosterone, estradiol, and progesterone, signaling through their respective steroid receptors, affect the functioning of immune cells to cause differential susceptibility to parasitic, bacterial, and viral infections. Microbes, including fungi, bacteria, parasites, and viruses, can also use sex steroid hormones and manipulate sex steroid receptor signaling mechanisms to increase their own survival and replication rate. The multifaceted use of sex steroid hormones by both microbes and hosts during infection forms the basis of this review. In the arms race between microbes and hosts, both hosts and microbes have evolved to utilize sex steroid hormone signaling mechanisms for survival.

Midtrimester amniotic fluid from healthy pregnancies has no microorganisms using multiple methods of microbiologic inquiry

“…54 The exogenous estrogen and progesterone in IVF treatment are associated with the risk of microbial invasion, because microbes can alter and use host hormones to facilitate growth and survival. 55 In addition, IVF women are exposed to more invasive operations, such as cervical excision procedures, hysteroscopic resection, induced abortion, and the IVF treatment itself, 56 which may be a route for MIAC. 24 In current study, it is hard to untangle the key contributors to the identification of 4 bacterial signals.…”

Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites

“…101 In addition to pathogenic bacteria, commensal bacteria in the gastrointestinal tract are responsive to and can even alter concentrations of sex steroids. 102,103 For example, adoptive transfer of gut commensals from male to female mice increases concentrations of androgens in females and alters the pathogenesis of autoimmune diseases. 102,103 Whether P4-based compounds, including the use of contraceptives alter the composition of the microbiome requires consideration.…”

“…102,103 For example, adoptive transfer of gut commensals from male to female mice increases concentrations of androgens in females and alters the pathogenesis of autoimmune diseases. 102,103 Whether P4-based compounds, including the use of contraceptives alter the composition of the microbiome requires consideration. Based on available data, it can be concluded that progestins protect against gastrointestinal infections by increasing host survival through their immunomodulatory effects.…”

Influenza in High-Risk Hosts—Lessons Learned from Animal Models

“…Hormonal variations between sexes have a marked impact on antiviral responses (Klein et al 2010; Vom Steeg and Klein 2019). Although influenza titers are largely similar between sexes, experimental influenza infection of male and female mice reveals a greater induction of proinflammatory cytokines and increased morbidity in female mice, whereas males show less production of humoral immune responses (Lorenzo et al 2011;Robinson et al 2011;Klein et al 2012;Vom Steeg and Klein 2017). This differential response to influenza infection is mitigated after gonadectomy, suggesting a role for sex hormones in the pathogenesis of influenza (Robinson et al 2011).…”

“…Interactions between hormones and immune mediators in systemic circulation and at the mother-fetal interface alter influenza pathogenesis in the pregnant host, as well as contribute to sex-based differences in the response to infection (Irving et al 2000;Raj et al 2014;van Riel et al 2016;Littauer and Skountzou 2018). Other comorbidities, including stress, depression, body mass index, aging, puberty, and exercise state, contribute to poor infection responses and can compound morbidity in pregnant hosts (Christian et al 2010;Avitsur et al 2011;Soydinc et al 2012;Christian 2014;Ingersoll 2017;Vom Steeg and Klein 2017).…”