Sabroe Ian, Dower Steven K, Whyte Moira K B
Division of Genomic Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK.
Clin Infect Dis. 2005 Nov 15;41 Suppl 7:S421-6. doi: 10.1086/431992.
Toll-like receptors (TLRs) play an essential role in the detection of invading pathogens and in the induction of host antimicrobial defenses. TLR4, the major endotoxin receptor, and TLR2, with agonists derived principally from gram-positive organisms, are likely to be important in the pathogenesis of sepsis. Both TLR2 and TLR4 agonists regulate important neutrophil functions, including adhesion, generation of reactive oxygen species, and release of chemokines, and activate major proinflammatory signaling pathways, including the nuclear factor- kappa B pathway. TLR stimulation produces only a modest direct inhibition of neutrophil apoptosis, although this signal is greatly amplified by the presence of monocytes, suggesting that regulation of the life span of neutrophils by TLR agonists may be principally mediated by responses of other endotoxin-responsive cells. We suggest that activation of neutrophils by TLRs is highly regulated, permitting acute neutrophil antimicrobial responses to TLR activation while providing a "brake" on inflammation by requiring the presence of mononuclear cells to significantly extend neutrophil survival.
Toll样受体（TLRs）在检测入侵病原体和诱导宿主抗菌防御方面发挥着至关重要的作用。主要的内毒素受体TLR4以及主要来源于革兰氏阳性菌的激动剂的TLR2，可能在脓毒症的发病机制中起重要作用。TLR2和TLR4激动剂均调节重要的中性粒细胞功能，包括黏附、活性氧的产生以及趋化因子的释放，并激活主要的促炎信号通路，包括核因子κB通路。TLR刺激仅对中性粒细胞凋亡产生适度的直接抑制作用，尽管单核细胞的存在会极大地放大该信号，这表明TLR激动剂对中性粒细胞寿命的调节可能主要由其他内毒素反应性细胞的反应介导。我们认为，TLRs对中性粒细胞的激活受到高度调节，允许中性粒细胞对TLR激活产生急性抗菌反应，同时通过要求单核细胞的存在来显著延长中性粒细胞的存活时间，从而对炎症起到“刹车”作用。
