Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1β, and,Immune complex deposition in the heart
Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1β, and,Immune complex deposition in the heart
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DOI：
10.4049/jimmunol.176.6.3516
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发表时间：
2006-03-15
影响因子：
4.4
通讯作者：
Rose, Noel R.
中科院分区：
文献类型：
--
作者：
Fairweather, DeLisa;Frisancho-Kiss, Sylvia;Rose, Noel R.
补体和补体受体（CR）通过启动入侵微生物的快速破坏，放大先天和适应性免疫反应，介导免疫复合物的溶解和清除，在免疫防御中发挥核心作用。C或CR表达缺陷与自身蛋白耐受性丧失和免疫复合物介导的自身免疫性疾病（如系统性红斑狼疮）的发展有关。在这项研究中，我们用CR1/2缺失的小鼠研究了CR在柯萨奇病毒B3 （CVB3）诱导的心肌炎中的作用。我们发现CR1/2缺乏显著增加急性CVB3心肌炎和心包纤维化，导致早期发展为扩张型心肌病和心力衰竭。炎症的增加不是由于病毒复制的增加，这在cr1 /2缺陷小鼠的心脏中没有显著改变，而是与巨噬细胞数量增加、il -1,6水平增加和心脏中免疫复合物沉积有关。补体调节蛋白cr1相关基因/蛋白Y （Crry）在心脏巨噬细胞群体中增加，而cr1 /2缺陷小鼠的脾脏中未成熟B220（低）B细胞在急性cvb3诱导的心肌炎中增加。这些结果表明，CR1/2的表达不是有效清除CVB3感染所必需的，而是阻止免疫介导的心脏损伤。
Complement and complement receptors (CR) play a central role in immune defense by initiating the rapid destruction of invading microorganisms, amplifying the innate and adaptive immune responses, and mediating solubilization and clearance of immune complexes. Defects in the expression of C or CR have been associated with loss of tolerance to self proteins and the development of immune complex-mediated autoimmune diseases such as systemic lupus erythematosus. In this study, we examined the role of CR on coxsackievirus B3 (CVB3)-induced myocarditis using mice deficient in CR1/2. We found that CR1/2 deficiency significantly increased acute CVB3 myocarditis and pericardial fibrosis resulting in early progression to dilated cardiomyopathy and heart failure. The increase in inflammation was not due to increased viral replication, which was not significantly altered in the hearts of CR1/2-deficient mice, but was associated with increased numbers of macrophages, IL-1,6 levels, and immune complex deposition in the heart. The complement regulatory protein, CR1-related gene/protein Y (Crry), was increased on cardiac macrophage populations, while immature B220(low) B cells were increased in the spleen of CR1/2-deficient mice during acute CVB3-induced myocarditis. These results show that expression of CR1/2 is not necessary for effective clearance of CVB3 infection, but prevents immune-mediated damage to the heart.