Sex Bias in the Outcome of Human Tropical Infectious Diseases: Influence of Steroid Hormones

Bernin, Hannah; Lotter, Hanna

doi:10.1093/infdis/jit610

Cited by 103 publications

(94 citation statements)

References 58 publications

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“…Furthermore, striking gender disparity in susceptibility to numerous autoimmune diseases with women more likely to develop SLE, RA, MS, and Sjogren's syndrome than men 9-, 3-, 6-and 9-fold, respectively, potentially implicates estrogen signaling in disease pathogenesis (58); however, the exact mechanisms linking ER function to autoimmunity remain poorly understood and are likely disease-specific. Conversely, reflecting heightened immune system function, females are reportedly less susceptible to viral, fungal, bacterial and parasitic infections than males (60,61). Furthermore, in murine models of sepsis, males are more prone to morbidity and display less robust immune response than proestrus females (62).…”

Section: Ncoas and Estrogen Receptors (Er␣ And Er␤)mentioning

confidence: 99%

Minireview: Nuclear Receptor Coregulators of the p160 Family: Insights into Inflammation and Metabolism

Rollins

Coppo

Rogatsky

2015

Molecular Endocrinology

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Nuclear receptor coactivators (NCOAs) are multifunctional transcriptional coregulators for a growing number of signal-activated transcription factors. The members of the p160 family (NCOA1/2/3) are increasingly recognized as essential and nonredundant players in a number of physiological processes. In particular, accumulating evidence points to the pivotal roles that these coregulators play in inflammatory and metabolic pathways, both under homeostasis and in disease. Given that chronic inflammation of metabolic tissues ("metainflammation") is a driving force for the widespread epidemic of obesity, insulin resistance, cardiovascular disease, and associated comorbidities, deciphering the role of NCOAs in "normal" vs "pathological" inflammation and in metabolic processes is indeed a subject of extreme biomedical importance. Here, we review the evolving and, at times, contradictory, literature on the pleiotropic functions of NCOA1/2/3 in inflammation and metabolism as related to nuclear receptor actions and beyond. We then briefly discuss the potential utility of NCOAs as predictive markers for disease and/or possible therapeutic targets once a better understanding of their molecular and physiological actions is achieved.

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Section: Ncoas and Estrogen Receptors (Er␣ And Er␤)mentioning

confidence: 99%

Minireview: Nuclear Receptor Coregulators of the p160 Family: Insights into Inflammation and Metabolism

Rollins

Coppo

Rogatsky

2015

Molecular Endocrinology

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“…Therefore, it is reasonable to presume that, to the extent steroids regulate the expression of transposable elements, this regulation could contribute to observed sex differences in mental disorders. To extend the hypothesis about schizophrenia, elaborated above, it could be argued that the earlier age of onset of this disease in males could be due to the underexplored immunosuppressive effects of androgens, which are at peak concentrations in the adolescent males at risk for a first psychotic episode (91,92). Alternately, it could be due to direct activation of ectopic retrotransposon expression by AR itself.…”

Section: Transposons: Controlling Elements After All?mentioning

confidence: 99%

Stress and the dynamic genome: Steroids, epigenetics, and the transposome

Hunter

Gagnidze

McEwen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

117

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Stress plays a substantial role in shaping behavior and brain function, often with lasting effects. How these lasting effects occur in the context of a fixed postmitotic neuronal genome has been an enduring question for the field. Synaptic plasticity and neurogenesis have provided some of the answers to this question, and more recently epigenetic mechanisms have come to the fore. The exploration of epigenetic mechanisms recently led us to discover that a single acute stress can regulate the expression of retrotransposons in the rat hippocampus via an epigenetic mechanism. We propose that this response may represent a genomic stress response aimed at maintaining genomic and transcriptional stability in vulnerable brain regions such as the hippocampus. This finding and those of other researchers have made clear that retrotransposons and the genomic plasticity they permit play a significant role in brain function during stress and disease. These observations also raise the possibility that the transposome might have adaptive functions at the level of both evolution and the individual organism.hippocampus | retrotransposon | histone marks | brain | genomic stress response

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“…The sex of the host influences the incidence of disease, parasite burden, pathology, mortality, and immunological response against various parasites, including Leishmania both in humans and in rodents (reviewed in [7–12]).…”

Section: Introductionmentioning

confidence: 99%

Gene-specific sex effects on eosinophil infiltration in leishmaniasis

et al. 2016

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BackgroundSex influences susceptibility to many infectious diseases, including some manifestations of leishmaniasis. The disease is caused by parasites that enter to the skin and can spread to the lymph nodes, spleen, liver, bone marrow, and sometimes lungs. Parasites induce host defenses including cell infiltration, leading to protective or ineffective inflammation. These responses are often influenced by host genotype and sex. We analyzed the role of sex in the impact of specific gene loci on eosinophil infiltration and its functional relevance.MethodsWe studied the genetic control of infiltration of eosinophils into the inguinal lymph nodes after 8 weeks of Leishmania major infection using mouse strains BALB/c, STS, and recombinant congenic strains CcS-1,-3,-4,-5,-7,-9,-11,-12,-15,-16,-18, and -20, each of which contains a different random set of 12.5% genes from the parental “donor” strain STS and 87.5% genes from the “background” strain BALB/c. Numbers of eosinophils were counted in hematoxylin-eosin-stained sections of the inguinal lymph nodes under a light microscope. Parasite load was determined using PCR-ELISA.ResultsThe lymph nodes of resistant STS and susceptible BALB/c mice contained very low and intermediate numbers of eosinophils, respectively. Unexpectedly, eosinophil infiltration in strain CcS-9 exceeded that in BALB/c and STS and was higher in males than in females. We searched for genes controlling high eosinophil infiltration in CcS-9 mice by linkage analysis in F2 hybrids between BALB/c and CcS-9 and detected four loci controlling eosinophil numbers. Lmr14 (chromosome 2) and Lmr25 (chromosome 5) operate independently from other genes (main effects). Lmr14 functions only in males, the effect of Lmr25 is sex independent. Lmr15 (chromosome 11) and Lmr26 (chromosome 9) operate in cooperation (non-additive interaction) with each other. This interaction was significant in males only, but sex-marker interaction was not significant. Eosinophil infiltration was positively correlated with parasite load in lymph nodes of F2 hybrids in males, but not in females.ConclusionsWe demonstrated a strong influence of sex on numbers of eosinophils in the lymph nodes after L. major infection and present the first identification of sex-dependent autosomal loci controlling eosinophilic infiltration. The positive correlation between eosinophil infiltration and parasite load in males suggests that this sex-dependent eosinophilic infiltration reflects ineffective inflammation.

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Sex Bias in the Outcome of Human Tropical Infectious Diseases: Influence of Steroid Hormones

Cited by 103 publications

References 58 publications

Minireview: Nuclear Receptor Coregulators of the p160 Family: Insights into Inflammation and Metabolism

Minireview: Nuclear Receptor Coregulators of the p160 Family: Insights into Inflammation and Metabolism

Stress and the dynamic genome: Steroids, epigenetics, and the transposome

Gene-specific sex effects on eosinophil infiltration in leishmaniasis

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