Sex differences in Coxsackievirus-induced myocarditis

描述(申请人提供)：心肌炎是一个重要的原因 在青少年和年轻人中心力衰竭的风险。而约33%的 心肌炎患者康复，其余患者可能发展为慢性扩张 心肌病，占北方所有心力衰竭的25% 美国。大约4%的人与CB3感染有关 心肌炎病例。CB3致小鼠心肌炎的研究进展 提供了关于适应性、获得性 自身免疫性心肌炎发病过程中对CB3的免疫应答 最近，我们研究了针对CB3的先天免疫反应的作用。 感染对心肌炎的发生和发展有显著影响 男性急性病毒性心肌炎和自身免疫性心肌炎水平增加。 尽管已知对CB3的适应性T细胞反应在 加剧男性疾病，对潜在的疾病知之甚少 决定性别差异的机制。这样做的目的是 应用是表征免疫和荷尔蒙的差异 男性和女性对CB3感染的免疫反应之间的差异 确定导致男性患病增加的因素。我们 假设CB3后早期激素和细胞因子环境 感染决定了后来的获得性免疫反应，导致 男性心肌炎增加。为了研究这一假设，我们 提出两个具体目标：(1)描述 男性和女性对CB3感染的免疫反应，以及(2)对 确定影响CB3免疫反应的激素因素 感染导致男性心肌炎严重程度增加。这个 这些研究产生的结果将有助于理解性别-- 基于此感染诱导模型中严重程度的差异 自身免疫性疾病。

DESCRIPTION (provided by applicant): Myocarditis is an important cause of heart failure among adolescents and young adults. While about 33% of myocarditis patients recover, the remainder may develop chronic dilated cardiomyopathy, which accounts for 25% of all heart failures in North America. CB3 infections have been implicated in around 4 % of myocarditis cases. Studies of CB3-induced myocarditis in mice have provided valuable information about the role of the adaptive, acquired immune response to CB3 in the development of autoimmune myocarditis. Recently we have examined the role of the innate immune response to CB3 infection on the development of myocarditis and have found significantly increased levels of acute viral and autoimmune myocarditis in males. Although the adaptive T cell response to CB3 is known to play a role in exacerbating disease in males, little is understood about the underlying mechanisms that determine the sex-based difference. The goal of this application is to characterize the immune and hormonal differences between the male and female immune response to CB3 infection in order to determine the factors that lead to increased disease in males. We hypothesize that the early hormonal and cytokine environment after CB3 infection determines the later adaptive immune response that results in increased myocarditis in males. To investigate this hypothesis, we propose two Specific Aims: (1) to characterize the differences between the male and female immune response to CB3 infection, and (2) to identify the hormonal factors that influence the immune response to CB3 infection resulting in increased severity of myocarditis in males. The findings generated by these studies will aid in understanding the sex- based differences in severity in this model of infection-induced autoimmune disease.