Massilamany Chandirasegaran, Gangaplara Arunakumar, Reddy Jay
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of health, Bethesda, MD.
Int J Cardiol. 2014 Dec 15;177(2):330-339. doi: 10.1016/j.ijcard.2014.09.136. Epub 2014 Oct 18.
Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of postinfectious myocarditis resembles that of human disease, making the observations made in animals relevant to humans. In this review, we discuss the complex nature of CVB3-induced myocarditis as it relates to the damage caused by both the virus and the host's response to infection. Based on recent data we obtained in the mouse model of CVB3 infection, we provide evidence to suggest that CVB3 infection accompanies the generation of cardiac myosin-specific CD4 T cells that can transfer the disease to naïve recipients. The therapeutic implications of these observations are also discussed.
心脏病是人类死亡的主要原因,而心肌炎是年轻成年人心力衰竭的一个主要原因。患有心肌炎的患者可能会发展为扩张型心肌病(DCM),这是心脏移植的常见原因,迄今为止,心脏移植是对抗DCM的唯一可行选择。心肌炎/DCM患者显示出针对柯萨奇病毒B(CVB)3和心脏抗原的抗体,提示CVB介导的自身免疫在疾病发病机制中起作用;然而,直接的因果关系仍有待临床确定。在实验中,使用CVB3的人类分离株可在易感小鼠品系中诱发心肌炎,感染后心肌炎的疾病发病机制与人类疾病相似,这使得在动物身上的观察结果与人类相关。在这篇综述中,我们讨论了CVB3诱导的心肌炎的复杂性质,因为它与病毒和宿主对感染的反应所造成的损害有关。基于我们最近在CVB3感染小鼠模型中获得的数据,我们提供证据表明,CVB3感染伴随着心脏肌球蛋白特异性CD4 T细胞的产生,这些细胞可将疾病传染给未感染的受体。我们还讨论了这些观察结果的治疗意义。