The physiological significance of innate immune signaling lies primarily in its role in host defense against invading pathogens. It is becoming increasingly clear that innate immune signaling also modulates the development of metabolic diseases, especially nonalcoholic fatty liver disease and cardiovascular diseases, which are characterized by chronic, low-grade inflammation due to a disarrangement of innate immune signaling. Notably, recent studies indicate that in addition to regulating canonical innate immune-mediated inflammatory responses (or immune-dependent signaling-induced responses), molecules of the innate immune system regulate pathophysiological responses in multiple organs during metabolic disturbances (termed immune-independent signaling-induced responses), including the disruption of metabolic homeostasis, tissue repair, and cell survival. In addition, emerging evidence from the study of immunometabolism indicates that the systemic metabolic status may have profound effects on cellular immune function and phenotypes through the alteration of cell-intrinsic metabolism. We summarize how the innate immune system interacts with metabolic disturbances to trigger immune-dependent and immune-independent pathogenesis in the context of nonalcoholic fatty liver disease, as representative of metabolic diseases, and cardiovascular diseases.

中文翻译：

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非酒精性脂肪肝疾病和心血管疾病的先天免疫信号。

先天免疫信号的生理意义主要在于其在宿主防御入侵病原体中的作用。越来越清楚的是，先天免疫信号还调节代谢性疾病的发展，特别是非酒精性脂肪肝疾病和心血管疾病，这些疾病的特征是由于先天免疫信号的紊乱引起的慢性低度炎症。值得注意的是，最近的研究表明，除了调节经典的先天性免疫介导的炎症反应（或免疫依赖性信号传导诱导的反应）外，先天性免疫系统的分子还调节代谢紊乱期间多个器官的病理生理反应（称为免疫独立性信号传导-诱导的反应），包括代谢稳态的破坏，组织修复，和细胞存活。此外，来自免疫代谢研究的新证据表明，系统代谢状态可能通过改变细胞内在代谢而对细胞免疫功能和表型产生深远影响。我们总结了非酒精性脂肪性肝病（以代谢性疾病和心血管疾病为代表）在先天性免疫系统如何与代谢紊乱相互作用以触发免疫依赖性和免疫非依赖性发病机理。