INNATE IMMUNITY IN VIRUS INDUCED AUTOIMMUNE MYOCARDITIS

病毒引起的自身免疫性心肌炎的先天免疫

• 批准号: 6078592
• 负责人: Noel R. Rose
• 金额: $ 16.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078592
• 关键词: Coxsackievirus; autoimmune disorder; bacterial disease; cytokine; disease /disorder etiology; disease /disorder model; enzyme linked immunosorbent assay; genetic strain; heart; histology; immunity; interferon gamma; interleukin 12; laboratory mouse; monoclonal antibody; myocarditis; natural killer cells; pathologic process; tumor necrosis factor alpha

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.

心肌炎是青少年和年轻人心力衰竭的重要原因。 虽然约33%的心肌炎患者康复，但其余患者可能发展为慢性扩张型心肌病，占北美所有心力衰竭的25%。 柯萨奇病毒B3（CB3）感染与约40%的心肌炎病例有关。抗病毒药物和免疫抑制疗法的结果喜忧参半，需要进一步研究以开发有效的疗法。 柯萨奇病毒诱导的小鼠心肌炎的研究提供了有价值的信息的作用，适应性，获得性免疫反应CB3的发展中的自身免疫性心肌炎。 最近，人们重新关注对感染的先天免疫应答如何影响适应性免疫的发展。 然而，很少有研究已经进行了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发展。 该建议的目的是描述“早期”细胞因子和先天免疫中涉及的免疫细胞在急性和慢性CB3诱导的心肌炎的发展中的作用。 我们推测，最初的先天免疫反应CB3决定是否适应性免疫反应导致后来的发展自身免疫性心肌炎。