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: 8116625
• 负责人: JENNIFER F NYLAND
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116625
• 关键词: Adult; Affect; Animal Model; Animals; Autoimmune Diseases; Autoimmune Process; Basic Science; Biological Markers; Brazil; Chronic Disease; Consumption; Coxsackie Viruses; Coxsackievirus Infections; Development; Dose; Environmental Exposure; Epidemiologic Studies; Event; Exposure to; Fetal Development; Fishes; Functional disorder; Genetic Predisposition to Disease; Goals; Heart Diseases; Immune response; Immune system; Infection; Infectious Agent; Link; Measurable; Mercury; Mining; Mus; Population; Prevalence; Risk; Risk Factors; Severities; Severity of illness; System; Testing; Translational Research; exposed human population; fetal; human disease; programs

The overall goal is to demonstrate a link between mercury (Hg) exposure and elevated risks of autoimmune disease. In this project, we will test two hypotheses in translational research linking basic research in an animal model of autoimmune disease and an ongoing epidemiological study in two Hg-exposed human populations in Amazonian Brazil. The hypotheses are that 1) exposure of mice to Hg, at low dose, can result in changes iti 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. While autoimmune diseases are recognized to involve both heritable and acquired risk factors, relatively littie Is known about the latter risks for human disease aside from exposure to infectious agents. These 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 in the context of ongoing environmental exposures (such as exposure to Hg). This project will assess programming changes that occur during the innate immune response to infection following exposure (during fetal development) to Hg, with an overall effect on the progression of coxsackievirus-induced autoimmune heart disease in mice and applying the biomarkers mined from these animal studies to a Hg-exposed human population in Amazonian Brazil (a riverine population exposed through fish consumption). Specific Aim 1. To test the hypothesis that fetal (murine) exposure to Hg induces changes in the immune system that affect the adult innate immune response to coxsackievirus infection and subsequent development of _ autoimmune disease. Specific Aim 2. 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.

总体目标是展示汞（HG）暴露与自身免疫风险升高之间的联系 疾病。在这个项目中，我们将在转化研究中检验两个假设，将动物的基础研究联系起来 自身免疫性疾病的模型和在两个暴露于HG的人群中正在进行的流行病学研究 亚马逊巴西。假设是1）小鼠暴露于低剂量时，可能会导致变化 对感染的先天免疫反应使最终感染后自身免疫性疾病在 严重程度和患病率和2）低剂量下的人类暴露于汞，可能导致变化 可以测量的免疫系统，表明自身免疫功能障碍的风险升高。自身免疫 疾病是美国最具破坏性的慢性疾病之一。识别自身免疫性疾病 要涉及可遗传和获得的风险因素，相对较小的人已经知道了人类的风险 疾病除了接触传染性药物外。据信这些会触发自身免疫的发展 疾病，但疾病的表达和严重程度可能反映了先前存在的遗传易感性 正在进行的环境暴露（例如接触HG）的背景。该项目将评估编程 在暴露后对先天免疫反应对感染的免疫反应期间发生的变化（胎儿期间 开发）到汞，对Coxsackievivirus诱导的自身免疫性心脏的进展产生了总体影响 小鼠的疾病，并将从这些动物研究开采的生物标志物应用于暴露于HG的人 亚马逊巴西的人口（通过鱼类消费暴露的河流人口）。 特定目的1。检验以下假设：胎儿（鼠）暴露于Hg会引起免疫系统的变化 这会影响成人先天免疫对Coxsackievivirus感染的反应以及随后的发展_ 自身免疫性疾病。具体目的2。检验以下假设：人类接触HG会诱发变化 可以测量的免疫系统，表明自身免疫功能障碍的风险升高。