INNATE IMMUNITY IN VIRUS-INDUCED AUTOIMMUNE MYOCARDITIS

心肌炎是青少年和年轻人心力衰竭的重要原因。虽然大约33%的心肌炎患者康复了，但其余的人可能会发展成慢性扩张型心肌病，这占北美所有心力衰竭的25%。大约40%的心肌炎病例与柯萨奇病毒B3(CB3)感染有关。抗病毒药物和免疫抑制疗法的结果好坏参半，需要进一步研究才能开发出有效的疗法。对柯萨奇病毒诱导的小鼠心肌炎的研究提供了关于对CB3的适应性获得性免疫反应在自身免疫性心肌炎发生中的作用的有价值的信息。最近，对感染的先天免疫反应如何影响获得性免疫的发展重新引起了人们的兴趣。然而，关于柯萨奇病毒感染的早期先天免疫反应如何影响自身免疫性心肌炎的研究很少。本研究的目的是阐明参与先天免疫的“早期”细胞因子和免疫细胞在CB3诱导的急性和慢性心肌炎发病中的作用。我们假设最初对CB3的先天免疫反应决定了获得性免疫反应是否导致自身免疫性心肌炎的后期发展。

Myocarditis is an important cause of heart failure among adolescents and young adults. While about 33 percent of myocarditis patients recover, the remainder may develop chronic dilated cardiomyopathy which accounts for 25 percent of all heart failures in North America. Coxsackievirus B3 (CB3) infections have been implicated in about 40 percent of myocarditis cases. Antiviral drugs and immunosuppressive therapies have given mixed results, requiring further research in order to develop effective therapies. Studies of Coxsackievirus-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, there has been renewed interest in how the innate immune response to infection may affect the development of adaptive immunity. However, very little research has been conducted on how the early, innate immune response to Coxsackievirus infection effects the development of autoimmune myocarditis. The aim of this proposal is to delineate the role of "early" cytokines and immune cells involved in innate immunity in the development of acute and chronic CB3-induced myocarditis. We hypothesize that the initial innate immune response to CB3 determines whether the adaptive immune response leads to the later development of autoimmune myocarditis.