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Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145231 | GEO | 2020/06/29

REPOSITORIES: GEO

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Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism.

Project description:Differences between female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. We previously reported that neutrophils from reproductive-age males are more immature and less activated than their female counterparts. To further characterize the mechanisms that drive differential neutrophil phenotypes, we performed RNA sequencing on circulating neutrophils from healthy adult females and males. Female neutrophils displayed significant up-regulation of type I IFN (IFN)-stimulated genes (ISGs). Single-cell RNA-sequencing analysis indicated that these differences are neutrophil specific, driven by a distinct neutrophil subset and related to maturation status. Neutrophil hyperresponsiveness to type I IFNs promoted enhanced responses to Toll-like receptor agonists. Neutrophils from young adult males had significantly increased mitochondrial metabolism compared to those from females and this was modulated by estradiol. Assessment of ISGs and neutrophil maturation genes in Klinefelter syndrome (47, XXY) males and in prepubescent children supported that differences in neutrophil phenotype between adult male and female neutrophils are hormonally driven and not explained by X chromosome gene dosage. Our results indicate that there are distinct sex differences in neutrophil biology related to responses to type I IFNs, immunometabolism, and maturation status that may have prominent functional and pathogenic implications.

| S-EPMC7368314 | biostudies-literature

Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism (bulkRNA-seq)

Project description:Differences in female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. The characterization of the mechanisms that drive differential neutrophil phenotypes between genders has been investigated. This provides new insights that distinct sex difference in neutrophil biology related to responses to type I IFNs, immunometabolism and maturation status that may have prominent functional and pathogenic implications. The transcriptome of neutrophils from healthy adult males and females was characterized using bulk RNASeq. The transcriptome of whole blood leukocytes was elucidated using scRNASeq.

2020-06-29 | GSE145229 | GEO

Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism (scRNA-seq)

2020-06-29 | GSE145230 | GEO

Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism

Project description:Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism

| PRJNA606470 | ENA

Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism (bulkRNA-seq)

Project description:Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism (bulkRNA-seq)

| PRJNA606473 | ENA

Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism (scRNA-seq)

Project description:Sex differences in neutrophil biology modulate response to type I Interferons and immunometabolism (scRNA-seq)

| PRJNA606472 | ENA

Guarding the frontiers: the biology of type III interferons.

Project description:Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs thereby help to maintain healthy mucosal surfaces through immune protection, without the significant immune-related pathogenic risk associated with type I IFN responses. Type III IFNs also target the human liver, with dual effects: they induce an antiviral state in hepatocytes, but specific IFN-λ4 action impairs the clearance of hepatitis C virus and could influence inflammatory responses. This constitutes a paradox that has yet to be resolved.

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Sex-Based Differences in Human Neutrophil Chemorepulsion.

Project description:A considerable amount is known about how eukaryotic cells move toward an attractant, and the mechanisms are conserved from Dictyostelium discoideum to human neutrophils. Relatively little is known about chemorepulsion, where cells move away from a repellent signal. We previously identified pathways mediating chemorepulsion in Dictyostelium, and here we show that these pathways, including Ras, Rac, protein kinase C, PTEN, and ERK1 and 2, are required for human neutrophil chemorepulsion, and, as with Dictyostelium chemorepulsion, PI3K and phospholipase C are not necessary, suggesting that eukaryotic chemorepulsion mechanisms are conserved. Surprisingly, there were differences between male and female neutrophils. Inhibition of Rho-associated kinases or Cdc42 caused male neutrophils to be more repelled by a chemorepellent and female neutrophils to be attracted to the chemorepellent. In the presence of a chemorepellent, compared with male neutrophils, female neutrophils showed a reduced percentage of repelled neutrophils, greater persistence of movement, more adhesion, less accumulation of PI(3,4,5)P3, and less polymerization of actin. Five proteins associated with chemorepulsion pathways are differentially abundant, with three of the five showing sex dimorphism in protein localization in unstimulated male and female neutrophils. Together, this indicates a fundamental difference in a motility mechanism in the innate immune system in men and women.

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Sex-based differences in human neutrophil chemorepulsion

Project description:Unstimulated male and female human neutrophil whole cell lysates. 867608-867612 M1-5 (male samples). 867613-867617 F1-F5 (female samples)

2022-02-17 | MSV000088857 | MassIVE

Sex differences in inflammation, redox biology, mitochondria and autoimmunity.

Project description:Autoimmune diseases are characterized by circulating antibodies and immune complexes directed against self-tissues that result in both systemic and organ-specific inflammation and pathology. Most autoimmune diseases occur more often in women than men. One exception is myocarditis, which is an inflammation of the myocardium that is typically caused by viral infections. Sex differences in the immune response and the role of the sex hormones estrogen and testosterone are well established based on animal models of autoimmune viral myocarditis as well as in mitochondrial function leading to reactive oxygen species production. RNA viruses like coxsackievirus B3, the primary cause of myocarditis in the US, activate the inflammasome through mitochondrial antiviral signaling protein located on the mitochondrial outer membrane. Toll-like receptor 4 and the inflammasome are the primary signaling pathways that increase inflammation during myocarditis, which is increased by testosterone. This review describes what is known about sex differences in inflammation, redox biology and mitochondrial function in the male-dominant autoimmune disease myocarditis and highlights gaps in the literature and future directions.

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