Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood–brain barrier leakage and a failure to restore cognitive–motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery.

创伤性脑损伤 (TBI) 和脑血管损伤是全球致残和死亡的主要原因。全身感染通常伴随这些疾病，并可能使结果恶化。脑损伤后的恢复取决于先天免疫，但感染对该过程的影响尚不清楚。在这里，我们证明全身引入的微生物和微生物产物以 I 型干扰素 (IFN-I) 依赖性方式干扰 TBI 后脑膜血管修复，连续感染促进慢性失修。从机制上讲，我们发现在 TBI 后遇到的依赖 MDA5 的沙粒病毒检测通过诱导 IFN-I 信号传导破坏了促血管生成骨髓细胞编程。全身性病毒感染同样会阻止颅内出血后脑实质中的恢复性血管生成，导致慢性 IFN-I 信号传导、血脑屏障渗漏和无法恢复认知 - 运动功能。我们的研究结果揭示了一种常见的免疫机制，通过这种机制，全身感染会在中枢神经系统损伤后偏离修复程序，并为改善恢复提供新的治疗靶点。