Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI) IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Bristol-Myers Squibb, Redwood City, CA 94063, USA.
Viruses. 2019 Sep 21;11(10):885. doi: 10.3390/v11100885.
Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the "fertile field" hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the "hygiene hypothesis", also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.
病毒感染是我们存在的自然组成部分。它们可以通过病毒病原体与我们的免疫系统相互作用，以多种方式影响我们。大多数情况下，由此产生的免疫反应对宿主是有益的。病原体被清除，从而保护我们的重要器官而没有其他后果。相反，我们的免疫系统对病原体的反应会导致器官损伤（免疫病理学）或导致自身免疫性疾病。迄今为止，有几种机制可导致病毒引起的自身免疫性疾病，包括分子模拟和旁观者激活，支持“肥沃领域”假说（在我们的综述中定义了术语）。相比之下，通过包括 Treg 激活和免疫偏离在内的机制，病毒感染与自身免疫的保护有关，支持“卫生假说”，这里也定义了这一假说。感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）就是其中一个原型，表明我们的免疫系统与病毒的相互作用既可以加速也可以预防自身免疫。使用 LCMV 小鼠模型进行的研究有助于构思和建立我们现在知道并用于解释病毒如何导致自身免疫激活或诱导耐受的几个概念。在 LCMV 感染过程中确定的一些最重要的机制在这篇简短的综述中进行了描述。
