Horwitz Marc S, Knudsen Maria, Ilic Alex, Fine Cody, Sarvetnick Nora
Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Viral Immunol. 2006 Winter;19(4):722-33. doi: 10.1089/vim.2006.19.722.
Clinical myocarditis is a precursor to dilated cardiomyopathy and a principal cause of heart failure. Nearly 30% of all recently diagnosed cases of myocarditis are attributable to infection with coxsackie B virus (CBV), the most frequently associated pathogen. CBV initially replicates in the pancreas and quickly spreads to the heart, inducing chronic autoimmunity. To determine whether immunosuppressive cytokines could act to limit the extent of autoimmunity to the heart, we infected transgenic mice that express immunosuppressive cytokines in the pancreas. Herein, we demonstrate that transgenic expression of transforming growth factor-beta (1) (TGF-beta) within the pancreatic beta cells prevented mice from developing autoimmune myocarditis after CBV infection. In contrast, transgenic expression of interleukin-4 did not inhibit virus-mediated heart disease. Furthermore, we show that TGF-beta expression reduced viral replication while promoting the recruitment of macrophages into the pancreas. These results illustrate the benefit of TGF-beta in controlling not only viral replication, but also CBV-mediated autoimmunity.
临床心肌炎是扩张型心肌病的先兆，也是心力衰竭的主要原因。在最近确诊的所有心肌炎病例中，近30% 归因于感染柯萨奇B病毒（CBV），这是最常相关的病原体。CBV最初在胰腺中复制，并迅速扩散到心脏，引发慢性自身免疫。为了确定免疫抑制细胞因子是否可以限制对心脏的自身免疫程度，我们感染了在胰腺中表达免疫抑制细胞因子的转基因小鼠。在此，我们证明胰腺β细胞内转化生长因子-β（1）（TGF-β）的转基因表达可防止小鼠在感染CBV后发生自身免疫性心肌炎。相比之下，白细胞介素-4的转基因表达并未抑制病毒介导的心脏病。此外，我们表明TGF-β表达减少了病毒复制，同时促进了巨噬细胞向胰腺的募集。这些结果说明了TGF-β不仅在控制病毒复制方面，而且在控制CBV介导的自身免疫方面的益处。
