Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA.
Department of Immunology, University of Washington, Seattle, WA, 98109, USA.
Curr Top Microbiol Immunol. 2023;442:155-174. doi: 10.1007/82_2020_204.
Neuroinvasive viral diseases are a considerable and growing burden on global public health. Despite this, these infections remain poorly understood, and the molecular mechanisms that govern protective versus pathological neuroinflammatory responses to infection are a matter of intense investigation. Recent evidence suggests that necroptosis, an immunogenic form of programmed cell death, may contribute to the pathogenesis of viral encephalitis. However, the receptor-interacting protein (RIP) kinases that coordinate necroptosis, RIPK1 and RIPK3, also appear to have unexpected, cell death-independent functions in the central nervous system (CNS) that promote beneficial neuroinflammation during neuroinvasive infection. Here, we review the emerging evidence in this field, with additional discussion of recent work examining roles for RIPK signaling and necroptosis during noninfectious pathologies of the CNS, as these studies provide important additional insight into the potential for specialized neuroimmune functions for the RIP kinases.
神经侵袭性病毒病对全球公共卫生构成了相当大且不断增长的负担。尽管如此，这些感染仍然知之甚少，并且控制感染后保护性与病理性神经炎症反应的分子机制是一个深入研究的课题。最近的证据表明，细胞程序性坏死的一种免疫原性形式——坏死性凋亡，可能有助于病毒性脑炎的发病机制。然而，协调坏死性凋亡的受体相互作用蛋白 (RIP) 激酶，即 RIPK1 和 RIPK3，在中枢神经系统 (CNS) 中似乎也具有出乎意料的、与细胞死亡无关的功能，可在神经侵袭性感染期间促进有益的神经炎症。在这里，我们回顾了这一领域的新证据，并额外讨论了最近研究检查 RIPK 信号和坏死性凋亡在 CNS 非传染性病变中的作用，因为这些研究为 RIP 激酶的特殊神经免疫功能提供了重要的额外见解。
