Social stress enhances sympathetic innervation of primate lymph nodes: Mechanisms and implications for viral pathogenesis
ABSTRACT 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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- "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. "
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.07/2013; 1(3):331-348. DOI:10.1177/2167702613478594
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- "Figure 6 provides a theoretical model that integrates existing results from human clinical studies relating SNS activity to indicators of HIV-1 pathogenesis (Ironson et al., in press), in vitro analyses of catecholamine effects on HIV- 1 replication (Cole et al., 1998; Cole et al., 1999; Collado et al., 2006;), and experimental analyses of the SIV lymphoid tissue model in vivo (Sloan et al., 2007). SNS activity is hypothesized to enhance viral replication by inhibiting the activity of Type I interferons (Collado et al., 2006; Sloan et al., 2007;), which increases viral replication through multiple mechanisms including impaired resistance to viral gene expression (via inhibition of the interferon-mediated antiviral state) (Collado et al., 2006) and enhanced cellular vulnerability to infection (via disinhibited expression of the viral coreceptors CCR5 and CXCR4, which occurs under physiologic conditions (Zang et al., 2001), but not in artificially stimulated cells (Yang et al., 2001). In conjunction with immune activation (e.g., via proinflammatory cytokines or ligation of the T cell receptor), these factors. "
ABSTRACT: Chronic Psychological stress (CPS) has several adverse effects both on HIV people and on HIV+patient. HIV-people with CPS are more susceptible to HIV infection than the HIV- people without CPS. T-cells have CXCR4 receptor and Macrophages have CCR5 receptor which can bind with both glucocorticoid and catecholamine hormone. HIV has GP120 residue which is able to bind with both CD4 and CXCR4/CCR5 receptor for its entry into the host cells. CPS increases glucocorticoid and catecholamine concentration in blood and thereby activates cAMP signaling pathway through binding the CXCR4/CCR5 receptors expressed on T cells and macrophages. This signal transduction pathway leads to the synthesis of more CXCR4 and CCR5 receptors by those cells, and in turn the cells become more susceptible to HIV infection. On HIV+patient stress hormones arrest the infected cell in G2 phase which is favorable for HIV replication. At the same time T-cells and macrophage are more susceptible to HIV, so HIV can infects a lot of immune cells and thereby makes the immune system weak. Stress also inhibits Th2 when the cell produces INF-γ as a response to viral attack. So that other cells remain vulnerable to viral infection. When T-cell count is decreased in the blood, the body cannot protect itself from other opportunistic infectious pathogens. As a result progression of AIDS increases rapidly.
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- "At the level of gene regulation, the CTRA profile underscores the fact that stress is not broadly immunosuppressive, but instead selectively suppresses some groups of immune response genes (e.g., Type I interferons and some immunoglobulin genes) while simultaneously activating others (e.g., pro-inflammatory cytokines) (Irwin and Cole, 2011). Adverse social conditions can also regulate gene expression in a wide variety of other tissues besides circulating leukocytes, including the central nervous system (Karelina et al., 2009; Karssen et al., 2007; Weaver et al., 2006) and peripheral lymphoid organs such as the lymph nodes and spleen (Cole et al., 2010; Sloan et al., 2007). Given the much smaller number of social genomics analyses targeting solid tissues, and the relative difficulty in ascertaining the functional significance of specific transcriptional alterations outside the well-charted territories of immune response, it is not yet clear what specific ''gene programs'' are being activated in these other tissue contexts (e.g., are these tissue ''defensive programs'' analogous to the leukocyte CTRA, or do they represent some other type of functional adaptation specific to the organ system involved?). "
ABSTRACT: Genomics-based analyses have provided deep insight into the basic biology of cancer and are now clarifying the molecular pathways by which psychological and social factors can regulate tumor cell gene expression and genome evolution. This review summarizes basic and clinical research on neural and endocrine regulation of the cancer genome and its interactions with the surrounding tumor microenvironment, including the specific types of genes subject to neural and endocrine regulation, the signal transduction pathways that mediate such effects, and therapeutic approaches that might be deployed to mitigate their impact. Beta-adrenergic signaling from the sympathetic nervous system has been found to up-regulated a diverse array of genes that contribute to tumor progression and metastasis, whereas glucocorticoid-regulated genes can inhibit DNA repair and promote cancer cell survival and resistance to chemotherapy. Relationships between socio-environmental risk factors, neural and endocrine signaling to the tumor microenvironment, and transcriptional responses by cancer cells and surrounding stromal cells are providing new mechanistic insights into the social epidemiology of cancer, new therapeutic approaches for protecting the health of cancer patients, and new molecular biomarkers for assessing the impact of behavioral and pharmacologic interventions.Brain Behavior and Immunity 11/2012; 30. DOI:10.1016/j.bbi.2012.11.008 · 6.13 Impact Factor