Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
Faculty of Veterinary and Agricultural Sciences, at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
Viruses. 2022 Nov 9;14(11):2476. doi: 10.3390/v14112476.
CNS viral infections are one of the major causes of morbidity and mortality worldwide and a significant global public health concern. Uncontrolled inflammation and immune responses in the brain, despite their protective roles, can also be harmful. The suppressor of cytokine signalling (SOCS) proteins is one of the key mechanisms controlling inflammatory and immune responses across all tissues including the brain. SOCS5 is highly expressed in the brain but there is little understanding of its role in the CNS. Using a mouse model of encephalitis, we demonstrate that lack of SOCS5 results in changes in the pathogenesis and clinical outcome of a neurotropic virus infection. Relative to wild-type mice, SOCS5-deficient mice had greater weight loss, dysregulated cytokine production and increased neuroinflammatory infiltrates composed predominantly of CD11b cells. We conclude that in the brain, SOCS5 is a vital regulator of anti-viral immunity that mediates the critical balance between immunopathology and virus persistence.
中枢神经系统病毒感染是全球发病率和死亡率的主要原因之一，也是一个重大的全球公共卫生关注点。尽管大脑中的炎症和免疫反应具有保护作用，但它们也可能造成伤害。细胞因子信号转导抑制蛋白（SOCS）是控制包括大脑在内的所有组织中炎症和免疫反应的关键机制之一。SOCS5 在大脑中高度表达，但对其在中枢神经系统中的作用知之甚少。通过使用脑炎的小鼠模型，我们证明 SOCS5 的缺乏会导致神经营养性病毒感染的发病机制和临床结果发生变化。与野生型小鼠相比，SOCS5 缺陷型小鼠的体重减轻更明显，细胞因子产生失调，并且神经炎症浸润增加，主要由 CD11b 细胞组成。我们得出结论，在大脑中，SOCS5 是抗病毒免疫的重要调节剂，介导免疫病理学和病毒持续存在之间的关键平衡。
