McGettrick Anne F, O'Neill Luke A J
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Br J Haematol. 2007 Oct;139(2):185-93. doi: 10.1111/j.1365-2141.2007.06802.x.
Toll-like receptors (TLRs) play a critical role in the induction of the immune response to invading pathogens. The detection of pathogens by TLRs initiates a signalling cascade that results in the activation of transcription factors such as nuclear factor (NF)-kappaB and interferon regulatory factors leading to the production of pro-inflammatory cytokines and type 1 interferons. Five cytoplasmic adaptors, MyD88, Mal, Trif, TRAM and SARM, are utilized by the TLRs to activate these signalling pathways. Through the years the main focus of research has been on the activation and function of TLRs in monocytic cells. This review discusses several additional roles of TLRs. TLR activation plays a role in influencing the differentiation of haematopoietic stem cells. Their activation also prevents apoptosis in neutrophils following pathogen invasion. B cells and T cells proliferation and differentiation is influenced by TLR activation and the possible therapeutic benefits of using TLR ligands for the treatment of chronic lymphocytic leukaemia will also be discussed.
Toll样受体(TLRs)在诱导针对入侵病原体的免疫反应中起关键作用。TLRs对病原体的检测启动了一个信号级联反应,导致转录因子如核因子(NF)-κB和干扰素调节因子的激活,从而导致促炎细胞因子和1型干扰素的产生。TLRs利用五种细胞质衔接蛋白MyD88、Mal、Trif、TRAM和SARM来激活这些信号通路。多年来,研究的主要重点一直是TLRs在单核细胞中的激活和功能。本综述讨论了TLRs的其他几个作用。TLR激活在影响造血干细胞的分化中起作用。它们的激活还可防止病原体入侵后中性粒细胞的凋亡。B细胞和T细胞的增殖和分化受TLR激活的影响,并且还将讨论使用TLR配体治疗慢性淋巴细胞白血病的潜在治疗益处。