Sexual Dimorphism and Gender in Infectious Diseases

Gay, Laetitia; Melenotte, Cléa; Lakbar, Inès; Mezouar, Soraya; Devaux, Christian; Raoult, Didier; Bendiane, Marc-Karim; Léone, Marc; Mège, Jean‐Louis

doi:10.3389/fimmu.2021.698121

Cited by 71 publications

(61 citation statements)

References 156 publications

(152 reference statements)

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“…As a result, these transgenic sheep exhibit a high tolerance to LPS challenge and also display enhanced resistance to the infectious disease, brucellosis, compared to WT [ 104 , 105 ]. Considering the higher reserve capacity for melatonin synthesis in women compared to in men, women seem to possess a significant advantage over men in tolerating stressful conditions, such as those of infectious diseases [ 106 ]. A current example is the obvious gender difference in SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

Tan

Hardeland

2021

Molecules

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In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of “reserve or maximum capacity of melatonin synthetic function” is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering ASMT/ASMTL genes in the pseudoautosomal region of sex chromosomes with high prevalence of mutation in males, as well as the sex bias of the mitochondria in which melatonin is synthesized, we hypothesize the existence of a dimorphism in melatonin production to favor females, which are assumed to possess a higher reserve capacity for melatonin synthesis than males. Under physiological conditions, this subtle dimorphism is masked by the fact that cells or tissues only need baseline melatonin production, which can be accomplished without exploiting the full potential of melatonin’s synthetic capacity. This capacity is believed to exceed the already remarkable nocturnal increase as observed within the circadian cycle. However, during aging or under stressful conditions, the reserve capacity of melatonin’s synthetic function is required to be activated to produce sufficiently high levels of melatonin for protective purposes. Females seem to possess a higher reserve/maximum capacity for producing more melatonin than males. Thus, this dimorphism of melatonin production becomes manifest and detectable under these conditions. The biological significance of the reserve/maximum capacity of melatonin’s synthetic function is to improve the recovery rate of organisms from injury, to increase resistance to pathogen infection, and even to enhance their chances of survival by maximizing melatonin production under stressful conditions. The higher reserve/maximum capacity of melatonin synthesis in females may also contribute to the dimorphism in longevity, favoring females in mammals.

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Section: Discussionmentioning

confidence: 99%

The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

Tan

Hardeland

2021

Molecules

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“…This will need a large cohort study, ideally using a larger number of tissues from the same COVID-19 patients. It is worth noting that sex hormones also regulate the innate and adaptive immune responses, which may play an additional role in the severity of COVID-19, related to the disparity of deaths between male and female populations [25].…”

Section: Discussionmentioning

confidence: 99%

A Plausible Link of TMPRSS2/ACE2/AR Signaling to Male Mortality during the COVID-19 Pandemic in the United States

Wong

Jiang

2021

Pathogens

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The COVID-19 pandemic continues around the world, where the United States is among the worst in terms of both morbidity and fatality of the viral infection. We aim to investigate the plausible link of tissue SARS-CoV-2 viral entry gene expression, such as TMPRSS2 and ACE2, with infection and death by gender during the COVID-19 pandemic in the United States. We find a significantly higher incidence of COVID-19 death in men than in women, even though SARS-CoV-2 infection in women is higher than in men. We discover that the expression of TMPRSS2 and ACE2 in intestine, but not in lung, tends to be positively associated with the incidence of SARS-CoV-2 infection in men. In contrast, the high incidence of death in men is negatively correlated with TMPRSS2/ACE2 expression in intestine. Strikingly, the correlation of TMPRSS2/ACE2 expression with SARS-CoV-2 infection and death is the opposite in females, compared with that in males. Interestingly, male hormone signaling seems to be involved in mortality, as the low expression of testosterone receptor AR in the prostate contributes to death in men according to age. These observations point to a plausible contribution of male hormone metabolism in the regulation of TMPRSS2/ACE2 signaling to fatality by SARS-CoV-2 infection in men.

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“…Men are at increased risk for most infections. The explanation for this observation is rather complex and involves both biological and social factors [100]. Sexual steroid hormones play an important role in susceptibility to infections through differential modulation of pro-inflammatory and anti-inflammatory cytokine expression, toll-like receptor expression, antibody production, metabolism, growth, and virulence of pathogenic bacteria [101].…”

Section: Gendermentioning

confidence: 99%

“…Sexual steroid hormones play an important role in susceptibility to infections through differential modulation of pro-inflammatory and anti-inflammatory cytokine expression, toll-like receptor expression, antibody production, metabolism, growth, and virulence of pathogenic bacteria [101]. Estrogens can enhance both cell-mediated and humoral immune responses, while progesterone and testosterone have anti-inflammatory effects and suppress innate immune responses [100][101][102]. Additionally, it seems that genetic factors related to sex chromosomes (X and Y) may play a part [103], and differences in occupational activities and lifestyle result in different exposures to pathogens [100].…”

Section: Gendermentioning

confidence: 99%

“…Estrogens can enhance both cell-mediated and humoral immune responses, while progesterone and testosterone have anti-inflammatory effects and suppress innate immune responses [100][101][102]. Additionally, it seems that genetic factors related to sex chromosomes (X and Y) may play a part [103], and differences in occupational activities and lifestyle result in different exposures to pathogens [100].…”

Section: Gendermentioning

confidence: 99%

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Risk Factors for Infections, Antibiotic Therapy, and Its Impact on Cancer Therapy Outcomes for Patients with Solid Tumors

Kubeček

Paterová

Novosadová

2021

Life

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Infections represent a significant cause of morbidity and mortality in cancer patients. Multiple factors related to the patient, tumor, and cancer therapy can affect the risk of infection in patients with solid tumors. A thorough understanding of such factors can aid in the identification of patients with substantial risk of infection, allowing medical practitioners to tailor therapy and apply prophylactic measures to avoid serious complications. The use of novel treatment modalities, including targeted therapy and immunotherapy, brings diagnostic and therapeutic challenges into the management of infections in cancer patients. A growing body of evidence suggests that antibiotic therapy can modulate both toxicity and antitumor response induced by chemotherapy, radiotherapy, and especially immunotherapy. This article provides a comprehensive review of potential risk factors for infections and therapeutic approaches for the most prevalent infections in patients with solid tumors, and discusses the potential effect of antibiotic therapy on toxicity and efficacy of cancer therapy.

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Sexual Dimorphism and Gender in Infectious Diseases

Cited by 71 publications

References 156 publications

The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

A Plausible Link of TMPRSS2/ACE2/AR Signaling to Male Mortality during the COVID-19 Pandemic in the United States

Risk Factors for Infections, Antibiotic Therapy, and Its Impact on Cancer Therapy Outcomes for Patients with Solid Tumors

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