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Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

ABSTRACT: Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

PROVIDER: PRJNA561344 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10009953.fastq.gz	Fastqsanger.gz
	SRR10009954.fastq.gz	Fastqsanger.gz
	SRR10009955.fastq.gz	Fastqsanger.gz
	SRR10009956.fastq.gz	Fastqsanger.gz
	SRR10009957.fastq.gz	Fastqsanger.gz

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Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

Project description:Social experiences are an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a pro-inflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here, we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB dependent pro-inflammatory pathways and lower expression of genes involved in the antiviral response and type I interferon (IFN) signaling (see Snyder-Mackler et al. Science, 2016 doi:10.1126/science.aah3580 and GSE83304). Here we show that, counter to predictions, low status drives more exaggerated expression of both NF-κB and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are not only linked to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history – in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

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Dramatic effects of social behavior on gene regulation in rhesus macaques

Project description:This SuperSeries is composed of the following subset Series: GSE33090: Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression] GSE34127: Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression] GSE34128: Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite_seq] Refer to individual Series

2012-02-01 | E-GEOD-34129 | biostudies-arrayexpress

Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques.

Project description:Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB-dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB- and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history-in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

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Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression]

Project description:Analysis of gene expression differences in relationship to dominance rank in female rhesus macaques. RNA obtained from isolated peripheral blood mononuclear cells from 49 adult female rhesus macaques of dominance ranks 1 (high) to 5 (low) across 10 social groups. Total 100 samples = (47 individuals X 2 replicates) + (2 individuals X 3 replicates)

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Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression]

Project description:Analysis of gene expression differences in relationship to dominance rank in female rhesus macaques. RNA obtained from 4 cell populations (helper T cells, cytotoxic T cells, monocytes, and B cells) from isolated peripheral blood mononuclear cells sampled from 5 adult female rhesus macaques across 5 different social groups and 5 different dominance ranks [dominance ranks : 1 = high, 5 = low]

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Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.

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2016-11-08 | GSE83304 | GEO

Social status alters immune regulation and response to infection [PBMC_ATACseq]

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Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression]

Project description:Analysis of gene expression differences in relationship to dominance rank in female rhesus macaques.

2012-02-01 | GSE33090 | GEO

Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression]

Project description:Analysis of gene expression differences in relationship to dominance rank in female rhesus macaques.

2012-02-01 | GSE34127 | GEO