SeXX Matters in Infectious Disease Pathogenesis

Steeg, Landon G. vom; Klein, Sabra L.

doi:10.1371/journal.ppat.1005374

Cited by 296 publications

(331 citation statements)

References 26 publications

Supporting

Mentioning

306

Contrasting

Unclassified

Order By: Relevance

“…KEYWORDS coxsackievirus B3, intestine, pathogenesis, sex hormones S ex contributes to the frequency and severity of many human diseases (1)(2)(3). Epidemiological studies show that men are more susceptible to bacterial, viral, and fungal infections (2).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Sex-Dependent Intestinal Replication of an Enteric Virus

Robinson

Wang

Pfeiffer

2017

J Virol

View full text Add to dashboard Cite

Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine. In light of recent studies identifying intestinal factors, such as the microbiota, that alter enteric viral replication, we sought to investigate coxsackievirus replication within the intestine. Here, we orally infected mice with coxsackievirus B3 (CVB3) and found that CVB3 replication in the intestine is sex dependent. CVB3 replicated efficiently in the intestine of male mice but not female mice. Additionally, we found that the type I interferon response and sex hormones can alter both viral replication and lethality. Overall, these data suggest that sex and the immune response play a vital role in CVB3 replication in the intestine and should be considered in light of the sex bias observed in human disease.IMPORTANCE Sex bias in severe sequelae from enteric viral infections has been observed. Since viruses have evolved to achieve optimal levels of fitness in their environmental niches, it is imperative to study viruses at the site of initial replication. Here, we used an oral inoculation system for CVB3, which follows the natural route of infection in the gastrointestinal tract. We found that sex can influence the replication of CVB3 in the intestine. Additionally, the type I interferon response and sex hormones alter both CVB3 intestinal replication and lethality. Overall this work highlights the fact that sex should be considered in investigations of enteric viral replication and pathogenesis.KEYWORDS coxsackievirus B3, intestine, pathogenesis, sex hormones S ex contributes to the frequency and severity of many human diseases (1-3). Epidemiological studies show that men are more susceptible to bacterial, viral, and fungal infections (2). Women, while more resistant to pathogens, are at an increased risk for autoimmune disorders. Sexual dimorphism in disease has been attributed to differential gene expression, sex hormones, and variations in immune function (4). However, sex as a variable in disease models is understudied, limiting our understanding of the mechanism of sex bias in various diseases.Coxsackievirus is a nonenveloped RNA virus from the Picornaviridae family and is implicated in a range of diseases (5-8). In humans, males are twice as likely as females to develop sequelae from coxsackievirus infection (9). While most coxsackievirus infections are self-limiting, they can cause severe disease. In particular, coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis, and extensive cardiac damage can lead to cardiac failure (10, 11). Because there are no current vaccines or ...

show abstract

mentioning

confidence: 99%

“…Epidemiological studies show that men are more susceptible to bacterial, viral, and fungal infections (2). Women, while more resistant to pathogens, are at an increased risk for autoimmune disorders.…”

mentioning

confidence: 99%

Sex-Dependent Intestinal Replication of an Enteric Virus

Robinson

Wang

Pfeiffer

2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Percentage women (%) 1 1 The percentage will vary depending on the age group studied (4) It is advantageous for women to have two X chromosomes. Women are protected against Xlinked hereditary diseases.…”

Section: Autoimmune Diseasementioning

confidence: 99%

Hvorfor er autoimmune sykdommer hyppigere hos kvinner?

Ørstavik¹

2017

Tidsskriftet

View full text Add to dashboard Cite

The author has completed the ICMJE form and reports no conflicts of interest.Women are less susceptible to infectious diseases than men, but are more often prone to autoimmune diseases. This higher prevalence is partly attributable to the X chromosome, which has many genes relating to the immune system. It is advantageous for women to have two X chromosomes, but the price is a greater tendency to develop autoimmunity. Illustration: Ørjan Jensen/SuperpopWomen are healthier and live longer than men. They are less susceptible to infectious diseases (1), but on the other hand 80% of individuals with autoimmune diseases are women. These diseases affect 5-10% of the population, are often chronic, and represent a considerable burden on healthcare budgets (2, 3).The autoimmune diseases are a heterogeneous group with multifactorial causes. The common denominator is an immunological reaction that leads to the breakdown, either systemic or organ-specific, of tolerance for the subject's own tissue. Most autoimmune

show abstract

“…Multiple sclerosis (MS) is no different, with women at a rate of 3:1, or 75%, compared to men (Confavreux et al 1998). It is known that male and female immune systems function differently, with the female immune system responding and clearing pathogens better than male immune systems (vom Steeg and Klein 2016). Additionally, females have more robust response to vaccines compared to males (Klein et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Estrogen protects both sexes against EAE by promoting common regulatory cell subtypes independent of endogenous estrogen

et al. 2017

View full text Add to dashboard Cite

Autoimmune diseases including multiple sclerosis predominantly affect females. Although high levels of sex hormones, particularly estrogen (E2), can reduce proinflammatory immune responses, it remains unclear if a lack of endogenous sex hormones might affect treatment with exogenous sex hormones. Pretreatment with E2 almost completely prevents intact female and male mice from developing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) by promoting various regulatory immune cell phenotypes. To evaluate the effects of exogenous estrogen in the absence of endogenous sex hormones, the current study compared EAE severity and the emergence of different immunoregulatory cell populations after E2 pretreatment of ovariectomized (OVX) female versus male mice. We found that E2 equally protected both OVX females and males from EAE over a 21 day observation period concomitant with reduced total cell numbers in spleen and spinal cord (males only), but enhanced percentages of CD19+CD5+CD1dhi, CD19+CD138+CD44hi and CD19+Tim-1+ Breg cells, CD8+CD122+ Treg cells and CD11b+206+ARG-1+ anti-inflammatory M2-like monocytes/macrophages in both groups. In contrast, E2 decreased the percentage of CD4+CD25+FoxP3+ Treg cells in OVX females but increased these Treg cells in males and intact female mice. These data suggest that with the exception of CD4+CD25+FoxP3+ Treg cells, E2 protection against EAE promotes highly overlapping immunoregulatory subsets in OVX females and males.

show abstract

SeXX Matters in Infectious Disease Pathogenesis

Cited by 296 publications

References 26 publications

Sex-Dependent Intestinal Replication of an Enteric Virus

Sex-Dependent Intestinal Replication of an Enteric Virus

Hvorfor er autoimmune sykdommer hyppigere hos kvinner?

Estrogen protects both sexes against EAE by promoting common regulatory cell subtypes independent of endogenous estrogen

Contact Info

Product

Resources

About