Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, United States.
Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, United States.
Elife. 2019 Jul 16;8:e47117. doi: 10.7554/eLife.47117.
Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.
共生微生物会影响中枢神经系统（CNS）的功能和发育；然而，人们对于微生物群在病毒引起的神经损伤中的作用知之甚少。我们发现，共生菌通过增强小胶质细胞的功能，有助于宿主在感染神经嗜性病毒后的防御。无菌小鼠或接受抗生素治疗的动物无法控制大脑内的病毒复制，从而导致瘫痪加重。来自无菌或用抗生素处理的动物的小胶质细胞不能刺激病毒特异性免疫，而小胶质细胞耗竭则导致脱髓鞘恶化。给感染病毒的无菌小鼠口服 Toll 样受体（TLR）配体可限制神经损伤。小胶质细胞的稳态激活依赖于 TLR4 的内在信号，因为 TLR4 在小胶质细胞内的破坏，而不是整个中枢神经系统（不包括小胶质细胞），会导致病毒引起的临床疾病增加。这项工作表明，肠道免疫刺激产物可以影响小胶质细胞的功能，以防止病毒感染后中枢神经系统损伤。
