Mercury exposure and the innate immune response in autoimmune heart disease

汞暴露与自身免疫性心脏病的先天免疫反应

• 批准号: 7224405
• 负责人: JENNIFER F NYLAND
• 金额: $ 9.06万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224405
• 关键词: Adult; Affect; Animal Model; Animals; Autoimmune Diseases; Autoimmune Process; Bacteria; Basic Science; Biological Markers; Brazil; Cardiovascular system; Chronic Disease; Complex; Coxsackie Viruses; Coxsackievirus Infections; Development; Disease; Dose; Epidemiologic Studies; Event; Exposure to; Fetal Development; Fetus; Functional disorder; Genetic Predisposition to Disease; Goals; Heart Diseases; Human; Immune; Immune response; Immune system; Infection; Infectious Agent; Left; Link; Measurable; Mercury; Mining; Mothers; Mus; Pathway interactions; Play; Population; Prevalence; Research; Research Personnel; Risk; Risk Factors; Role; Severities; Severity of illness; Testing; Translational Research; Virus; exposed human population; fetal; fetal programming; human disease; programs

DESCRIPTION (provided by applicant) The overall goal is to demonstrate a link between mercury (Hg) exposure and elevated risks of autoimmune disease. In this project, the investigators will test two hypotheses in translational research linking basic research in an animal model of autoimmune disease and a pilot epidemiological study in a Hg-exposed human population in Amazonian Brazil. The hypotheses are that: 1) exposure of mice (adults and fetuses) to Hg, at low dose, can result in changes in the innate immune response to infection such that ultimately post-infection autoimmune disease is exacerbated in terms of severity and prevalence and 2) exposure of humans to Hg, at low dose, can result in changes in the immune system that are measurable and indicative of elevated risk of autoimmune dysfunction. Autoimmune diseases are among the most devastating chronic diseases in the US, affecting nearly 50 million people. While autoimmune diseases are generally recognized to involve both heritable and acquired risk factors, relatively little is known about the latter risks for human disease aside from exposure to infectious agents, such as viruses and bacteria. These infectious agents are believed to trigger the development of autoimmune diseases, but the expression and severity of disease may be a reflection of pre-existing genetic susceptibility. This project will assess programming changes that occur during the innate immune response to infection following exposure (either at adulthood or during fetal development) to Hg, with an overall effect on the progression of Coxsackie virus-induced autoimmune heart disease in mice and apply the biomarkers mined from the studies in animals to a Hg-exposed human population in Amazonian Brazil. Specific Aim 1: To test the hypothesis that adult (murine) exposure to Hg induces changes in the innate immune response to Coxsackie virus infection, which result in exacerbation of subsequent autoimmune heart disease. Specific Aim 2: To test the hypothesis that fetal (murine) exposure to Hg induces changes in the immune system that are long lasting and that these early events affect the innate immune response to Coxsackie virus infection and the subsequent development of autoimmune heart disease in adulthood. Specific Aim 3: To test the hypothesis that human exposure to Hg induces changes in the immune system that are measurable and indicative of elevated risk of autoimmune dysfunction.

描述（由申请人提供） 总体目标是展示汞（HG）暴露与自身免疫性疾病风险升高之间的联系。在该项目中，研究人员将在转化研究中检验两个假设，该假设将自身免疫性疾病动物模型和亚马逊巴西汞含量暴露的人口中的试验性流行病学研究联系起来。假设是：1）在低剂量下，小鼠（成人和胎儿）暴露于Hg可能会导致对感染的先天免疫反应的变化，从而最终导致感染后自身免疫性疾病加剧，并且因严重性和患者的严重性和2）对HG的暴露量会导致无效，而在低剂量上的风险，导致量度的变化，导致量度的变化，导致量度的变化，而不是剂量的变化。功能障碍。 自身免疫性疾病是美国最具破坏性的慢性疾病之一，影响了近5000万人。 尽管通常认为自身免疫性疾病涉及可遗传和可获得的危险因素，但除了暴露于传染性药物（例如病毒和细菌）外，后一种人类疾病的风险相对较少。据信这些传染性药物会引发自身免疫性疾病的发展，但是疾病的表达和严重程度可能反映了现有的遗传敏感性。该项目将评估在暴露后对感染的先天免疫反应（成年后或胎儿发育期间）对HG的先天免疫反应发生的变化，这对Coxsackie病毒诱导的小鼠自身免疫性心脏病的进展产生了总体影响，并应用了来自Aprazonian Brazil HG暴露于HG暴露于HG的人群的生物标志物。 具体目的1：检验成年人（鼠）暴露于HG的假设会引起对Coxsackie病毒感染的先天免疫反应的变化，从而加剧了随后的自身免疫性心脏病。 具体目的2：检验以下假设：胎儿（鼠）暴露于HG会引起免疫系统的变化，这些变化持续了持久，并且这些早期事件会影响对Coxsackie病毒感染的先天免疫反应，以及随后在成年后的自身免疫性心脏病的发展。 特定目的3：检验以下假设：人类对HG的暴露会诱导免疫系统的变化，这些变化是可测量的，表明自身免疫性功能障碍的风险升高。