Sex differences in Coxsackievirus-induced myocarditis

描述（由申请人提供）：心肌炎是一个重要的原因 青少年和年轻人的心力衰竭。 而约33%的 心肌炎患者痊愈后，其余可发展为慢性扩张性心肌炎。 心肌病，占北卡罗来纳州所有心力衰竭的25% 美国参考 CB 3感染涉及约4%的 心肌炎病例。 在小鼠中进行的CB 3诱导的心肌炎的研究 提供了关于适应性、获得性和 自身免疫性心肌炎发展中对CB 3的免疫应答 最近，我们研究了先天性免疫反应对CB 3的作用， 感染对心肌炎的发展有显著影响 男性急性病毒性和自身免疫性心肌炎水平升高。 尽管已知对CB 3的适应性T细胞应答在免疫调节中起作用， 在男性中加重疾病，对潜在的 决定性别差异的机制。 这个目标 应用是表征免疫和激素差异 男性和女性对CB 3感染的免疫反应之间的差异， 确定导致男性疾病增加的因素。 我们 假设CB 3后的早期激素和细胞因子环境 感染决定了后来的适应性免疫反应， 男性心肌炎增加。 为了研究这个假设，我们 提出了两个具体目标：（1）描述之间的差异 男性和女性对CB 3感染的免疫应答，以及（2）对 确定影响对CB 3免疫反应的激素因素 感染导致男性心肌炎严重程度增加。 的 这些研究的结果将有助于了解性别- 在这个模型中， 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.