Social Stress Enhances Sympathetic Innervation of Primate Lymph Nodes: Mechanisms and Implications for Viral Pathogenesis

Department of Psychology, University of California, Davis, Davis, California, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 09/2007; 27(33):8857-65. DOI: 10.1523/JNEUROSCI.1247-07.2007
Source: PubMed


Behavioral processes regulate immune system function in part via direct sympathetic innervation of lymphoid organs, but little is known about the factors that regulate the architecture of neural fibers in lymphoid tissues. In the present study, we find that experimentally imposed social stress can enhance the density of catecholaminergic neural fibers within axillary lymph nodes from adult rhesus macaques. This effect is linked to increased transcription of the key sympathetic neurotrophin nerve growth factor and occurs predominately in extrafollicular regions of the paracortex that contain T-lymphocytes and macrophages. Functional consequences of stress-induced increases in innervation density include reduced type I interferon response to viral infection and increased replication of the simian immunodeficiency virus. These data reveal a surprising degree of behaviorally induced plasticity in the structure of lymphoid innervation and define a novel pathway by which social factors can modulate immune response and viral pathogenesis.

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Available from: John P Capitanio, Jan 23, 2016
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    • "Recently, Cole [31] found that subjective measures of health are better predictors of disease and mortality since perceptions and social factors affect gene expression. Social stimuli and perceptions of social conditions seem to regulate the expression of neural genes such as the nerve growth factor gene [32] the glucocorticoid receptor gene [33] the key immune system genes [32] and leukocytes [33]. These findings show that individuals' perceptions of their health result in changes in their genes, where more positive subjective appraisals of health relate to more favorable clinical/objective health outcomes. "
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    ABSTRACT: Background To identify levels of physical inactivity and smoking and examine their relationships to health among older people in India. Methods In 2010, Longitudinal Aging Study in India researchers interviewed 1,683 older adults in randomly sampled households with members aged ≥ 45 years in eight stratified districts in four states (90.9% response rate). We first used descriptive analyses to characterize older people in poor and good health. Differences between groups were established using chi-squared and t-tests. Multivariate logistic regression analyses were then performed to determine whether physical inactivity and smoking led to poor health while controlling for district of residence, caste, age, gender, marital status, and educational level. Regression analyses were also used to identify significant relationships between socio-demographic characteristics and health behaviors. Results Larger proportions of older people in poor health were smokers (26.1% vs. 16.9%; p ≤ 0.001) and physically inactive (vigorous activities: 88.7% vs. 70.7%, p ≤ 0.001; moderate activities: 67.1% vs. 57.1%, p ≤ 0.01). Smoking (p ≤ 0.05) and lack of vigorous physical activity (p ≤ 0.001) increased the likelihood of poor health. Low educational level was significantly related to smoking and the lack of moderate physical activity (both p ≤ 0.001). Female gender decreased the likelihood of smoking. Male gender increased the likelihood of vigorous physical activity but decreased the likelihood of moderate physical activity. Conclusions Smoking and physical inactivity have important impacts on the health of older people in India. Policy attention is needed to improve these modifiable health behaviors.
    Full-text · Article · May 2014 · BMC Public Health
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    • "For example, recent studies have found that both a general tendency to be unsociable and exposure to 3 weeks of social instability upregulate expression of the gene that codes for nerve growth factor beta (NGF) in rhesus macaque lymph nodes (Sloan et al., 2007; Sloan et al., 2008). This is critical because upregulated NGF expression has been associated with reduced antiviral immune response gene expression in leukocytes , which increases an organism's vulnerability to viral infection (Collado-Hidalgo et al., 2006; Sloan et al., 2007). These dynamics have also been shown to trigger increased arborization of sympathetic nervous system fibers in the lymph node, which expands the regulatory pipeline from the brain to the immune system, making local leukocyte immune response gene and NGF transcription increasingly sensitive to social-environmental input. "
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    ABSTRACT: Although we generally experience our bodies as being biologically stable across time and situations, an emerging field of research is demonstrating that external social conditions, especially our subjective perceptions of those conditions, can influence our most basic internal biological processes-namely, the expression of our genes. This research on human social genomics has begun to identify the types of genes that are subject to social-environmental regulation, the neural and molecular mechanisms that mediate the effects of social processes on gene expression, and the genetic polymorphisms that moderate individual differences in genomic sensitivity to social context. The molecular models resulting from this research provide new opportunities for understanding how social and genetic factors interact to shape complex behavioral phenotypes and susceptibility to disease. This research also sheds new light on the evolution of the human genome and challenges the fundamental belief that our molecular makeup is relatively stable and impermeable to social-environmental influence.
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    • "Thus, one goal was to investigate the strength of the association between the genotype and reactivity in normal mother-reared monkeys, evaluated both in an undisturbed setting and under moderate challenge induced by relocation. Prior primate studies have shown the potency of relocation to a novel cage or social group as a probe of emotional reactivity (Capitanio & Lerche 1998; Sloan et al. 2007; Willette et al. 2007). "
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    ABSTRACT: Individual variation in serotonergic function is associated with reactivity, risk for affective disorders, as well as an altered response to disease. Our study used a nonhuman primate model to further investigate whether a functional polymorphism in the promoter region for the serotonin transporter gene helps to explain differences in proinflammatory responses. Homology between the human and rhesus monkey polymorphisms provided the opportunity to determine how this genetic variation influences the relationship between a psychosocial stressor and immune responsiveness. Leukocyte numbers in blood and interleukin-6 responses are sensitive to stressful challenges and are indicative of immune status. The neutrophil-to-lymphocyte ratio and cellular interleukin-6 responses to in vitro lipopolysaccharide stimulation were assessed in 27 juvenile male rhesus monkeys while housed in stable social groups (N(LL) =16, N(S) =11) and also in 18 animals after relocation to novel housing (N(LL) =13, N(S) =5). Short allele monkeys had significantly higher neutrophil-to-lymphocyte ratios than homozygous Long allele carriers at baseline (t(25)=2.18, p=0.02), indicative of an aroused state even in the absence of disturbance. In addition, following the housing manipulation, interleukin-6 responses were more inhibited in short allele carriers (F(1,16)=8.59, p=0.01). The findings confirm that the serotonin transporter gene-linked polymorphism is a distinctive marker of reactivity and inflammatory bias, perhaps in a more consistent manner in monkeys than found in many human studies.
    No preview · Article · Jan 2013 · Genes Brain and Behavior
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