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: 7324847
• 负责人: JENNIFER F NYLAND
• 金额: $ 8.84万
• 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/7324847
• 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; Risk; Risk Factors; Role; Severities; Severity of illness; Testing; Translational Research; Virus; exposed human population; fetal; fetal programming; 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 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 expressio'n 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 Coxsackievirus-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 Coxsackievirus 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 Coxsackievirus 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.

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，将基础研究联系起来 自身免疫性疾病的动物模型和一项在汞暴露的人群中的试验性流行病学研究 亚马逊巴西。假设是1）小鼠（成人和胎儿）暴露于低剂量的汞，可以 导致对感染的先天免疫反应的变化，从而最终自身免疫后自动免疫 疾病因严重程度和患病率而加剧，2）人类暴露于Hg，低剂量， 可以导致免疫系统的变化，该免疫系统可测量并表明升高的风险 自身免疫功能障碍。自身免疫性疾病是最具破坏性的慢性疾病之一 美国，影响了近5000万人。通常认为自身免疫性疾病既涉及 可遗传和获得的风险因素，关于后一种人类疾病的风险相对较少 从暴露于传染剂，例如病毒和细菌。这些感染者被认为是 触发自身免疫性疾病的发展，但疾病的表现和严重程度可能是 现有遗传敏感性的反射。该项目将评估发生的编程更改 在接触后对感染的先天免疫反应期间（成年时或胎儿期间 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，并将从动物研究中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。 特定目的1。测试成年人（鼠）暴露于HG的假设会引起先天的变化 对Coxsackievivirus感染的免疫反应，这导致随后的自身免疫性心脏加剧 疾病。 特定目的2。检验以下假设：胎儿（鼠）暴露于Hg会引起免疫变化 持久的系统，这些早期事件会影响对先天性的免疫反应 Coxsackievivirus感染和成年后自身免疫性心脏病的随后发展。 特定目的3。检验以下假设：人类接触HG会引起免疫系统的变化 可测量的，表明自身免疫功能障碍的风险升高。

项目成果

Novel biomarkers of mercury-induced autoimmune dysfunction: a cross-sectional study in Amazonian Brazil.

汞引起的自身免疫功能障碍的新型生物标志物：巴西亚马逊地区的一项横断面研究。

• DOI: 10.1016/j.envres.2014.03.024
• 发表时间: 2014
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Motts,JonathanA;Shirley,DevonL;Silbergeld,EllenK;Nyland,JenniferF
• 通讯作者: Nyland,JenniferF

Fetal and maternal immune responses to methylmercury exposure: a cross-sectional study.

胎儿和母体对甲基汞暴露的免疫反应：一项横断面研究。

• DOI: 10.1016/j.envres.2011.02.010
• 发表时间: 2011
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Nyland,JenniferF;Wang,SusieB;Shirley,DevonL;Santos,ElisabethO;Ventura,AnaMaria;deSouza,JoseM;Silbergeld,EllenK
• 通讯作者: Silbergeld,EllenK

Biomarkers of methylmercury exposure immunotoxicity among fish consumers in Amazonian Brazil.

• DOI: 10.1289/ehp.1103741
• 发表时间: 2011-12
• 期刊: Environmental health perspectives
• 影响因子: 10.4
• 作者: Nyland JF;Fillion M;Barbosa F Jr;Shirley DL;Chine C;Lemire M;Mergler D;Silbergeld EK
• 通讯作者: Silbergeld EK