Mullick Adam E, Tobias Peter S, Curtiss Linda K
Department of Immunology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Immunol Res. 2006;34(3):193-209. doi: 10.1385/IR:34:3:193.
The identification of Toll-like receptors (TLRs) as key patternrecognition receptors of innate immunity has opened inquiries into previously unknown disease mechanisms. The ability of TLRs to detect a spectrum of pathogen-derived molecules defines their importance in innate immunity and provides a mechanistic link between infection and disease. Atherosclerosis is a chronic inflammatory disease where immune and metabolic factors interact to initiate and propagate arterial lesions. An understanding of TLRs in atherosclerosis could clarify the etiology of this complex process. Furthermore, the existence of host-derived endogenous TLR ligands may implicate TLR involvement in disease mechanisms beyond innate immunity, such as a role in homeostatic mechanisms to resolve injury. Our current knowledge of TLRs in atherosclerosis is discussed in this review with emphasis on experimental studies in atherosclerosis-susceptible mouse models. Highlights from studies of TLR involvement in other disease processes have demonstrated that TLR-dependent mechanisms probably parallel those found in atherosclerosis, some of which could be important in mitigating atherosclerotic injury. Finally, an appreciation of the pro- and anti-atherosclerotic mechanisms of TLR activation over the entire lifetime of an organism will provide clues to the role of TLRs in both health and disease.
Toll样受体（TLRs）作为固有免疫的关键模式识别受体，开启了对以前未知疾病机制的探究。TLRs检测一系列病原体衍生分子的能力，决定了它们在固有免疫中的重要性，并在感染与疾病之间提供了一种机制联系。动脉粥样硬化是一种慢性炎症性疾病，免疫和代谢因素相互作用以启动和传播动脉病变。了解动脉粥样硬化中的TLRs有助于阐明这一复杂过程的病因。此外，宿主来源的内源性TLR配体的存在，可能意味着TLRs参与了固有免疫之外的疾病机制，比如在解决损伤的稳态机制中发挥作用。本综述讨论了我们目前对动脉粥样硬化中TLRs的认识，重点是对动脉粥样硬化易感小鼠模型的实验研究。TLRs参与其他疾病过程的研究亮点表明，TLR依赖的机制可能与动脉粥样硬化中的机制相似，其中一些机制可能对减轻动脉粥样硬化损伤很重要。最后，了解生物体整个生命周期中TLR激活的促动脉粥样硬化和抗动脉粥样硬化机制，将为TLRs在健康和疾病中的作用提供线索。
