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.
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.
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.
Project description:Social status is one of the strongest predictors of human disease risk and mortality, and it also influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined genomics with a social status manipulation in female rhesus macaques to investigate how status alters immune function. We demonstrate causal but largely plastic social status effects on immune cell proportions, cell type-specific gene expression levels, and the gene expression response to immune challenge. Further, we identify specific transcription factor signaling pathways that explain these differences, including low-status-associated polarization of the Toll-like receptor 4 signaling pathway toward a proinflammatory response. Our findings provide insight into the direct biological effects of social inequality on immune function, thus improving our understanding of social gradients in health.