Innate immunity and toll-like receptors: Clinical implications of basic science research
Innate immunity and toll-like receptors: Clinical implications of basic science research
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DOI：
10.1016/j.jpeds.2004.01.057
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发表时间：
2004-04-01
影响因子：
5.1
通讯作者：
Arditi, M
中科院分区：
文献类型：
--
作者：
Abreu, MT;Arditi, M
人类经常接触各种可能引起感染的微生物。在自卫中，人类宿主进化出了复杂的保护机制，Toll 样受体 (TLR) 已成为防御的中心点。这些受体结合微生物表达但人类宿主不表达的分子结构，例如脂多糖（LPS）或双链RNA（dsRNA）。这些受体的激活会引发炎症级联反应，试图清除致病病原体并启动特定的适应性免疫反应。病原体感知缺陷可能使宿主容易反复感染。然而，这些先天免疫缺陷综合征相对罕见，这说明先天免疫系统对病原体的感知存在冗余。更常见的是，TLR4 的多态性与严重和复发性感染的易感性增加有关，但由于炎症减少而可以预防动脉粥样硬化疾病。 Toll 样受体信号传导还可能促进疾病的病理生理学，并通过激活有害的免疫反应（例如败血症或炎症性肠病 (IBD)）来伤害宿主。本文的重点是描述 TLR 在健康和疾病的先天免疫反应中的作用。
Humans are constantly exposed to a wide variety of microorganisms that can cause infection. In self-defense, the human host has evolved complex protective mechanisms, and Toll-like receptors (TLRs) have emerged as a central point in defense. These receptors bind molecular structures that are expressed by microbes but are not expressed by the human host, eg, lipopolysaccharides (LPS) or double-stranded RNA (dsRNA). Activation of these receptors initiates an inflammatory cascade that attempts to clear the offending pathogen and set in motion a specific adaptive immune response. Defects in sensing of pathogens may predispose the host to recurrent infections. The relative rarity of these syndromes of defective innate immunity, however, speaks to the redundancy in sensing of pathogens by the innate immune system. More common, polymorphisms in TLR4 are associated with increased predisposition to severe and recurrent infections but protection against atherosclerotic disease due to diminished inflammation. Toll-like receptor signaling may also contribute to the pathophysiology of disease and injure the host by activating a deleterious immune response such as in sepsis or inflammatory bowel disease (IBD). The focus of this article is to describe the role of TLRs in the innate immune response in health and disease.