Basic and translational understandings of microbial recognition by toll-like receptors in the intestine.
Basic and translational understandings of microbial recognition by toll-like receptors in the intestine.
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DOI：
10.5056/jnm.2011.17.1.28
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发表时间：
2011-01
影响因子：
3.4
通讯作者：
Rhee SH
中科院分区：
文献类型：
--
作者：
Rhee SH
多细胞生物的微生物识别最初是由一组模式识别受体完成的，这些受体专门识别微生物相关的分子模式（MAMPs），如脂多糖、细菌脂蛋白、CpG DNA基序、双链RNA和鞭毛蛋白。toll样受体（TLRs）是典型的模式识别受体，TLRs对微生物的识别引起先天和炎症反应。目前在人类基因组中已经鉴定出10个TLR家族成员，大量研究发现，MAMPs-TLR接合的细胞内反应是由至少4个直接接头分子参与介导的，如髓样分化主要反应基因-88 (MyD88)， MyD88接头样（Mal）（也称为Toll/IL-1受体结构域含接头蛋白[TIRAP]），含有Toll/IL-1受体结构域的适配器诱导干扰素-β (TRIF)和TRIF相关适配器分子（TRAM）可激活转录因子，包括核因子κB、激活蛋白-1和干扰素调节因子。由于大量共生菌群持续存在于肠道内，因此tlr在肠上皮上的肠道微生物识别对调节肠道内稳态具有重要影响。事实上，TLR4和TLR5的异常激活在病因学上与肠道炎症性疾病（包括炎症性肠病和坏死性小肠结肠炎）的发生和进展有关。在这篇综述文章中，我们介绍了TLRs引发细胞内信号转导的分子机制，并总结了TLRs与胃肠道相关的生理相关性。
Microbial recognition by multicellular organisms is initially accomplished by a group of pattern recognition receptors which are specialized to recognize microbe-associated molecular patterns (MAMPs) such as lipopolysaccharide, bacterial lipoprotein, CpG DNA motif, double strand RNA and flagellin. Toll-like receptors (TLRs) are the representative pattern recognition receptors, and microbial recognition by TLRs elicits innate and inflammatory responses. Ten TLR family members have been presently identified in human genome, and numerous studies discovered that intracellular responses from MAMPs-TLR engagements are mediated by a participation of at least 4 immediate adaptor molecules such as myeloid differentiation primary response gene-88 (MyD88), MyD88 adaptor-like (Mal) (also known as Toll/IL-1 receptor domain-containing adaptor protein [TIRAP]), Toll/IL-1 receptor domain-containing adaptor-inducing interferon-β (TRIF) and TRIF-related adaptor molecule (TRAM) leading to activate transcription factors including nuclear factor κB, activator protein-1 and interferon-regulatory factors. Given that large amounts of commensal microbiota constantly reside in the intestinal lumen, enteric microbial recognition by TLRs at the intestinal epithelium provides a critical impact on regulating intestinal homeostasis. Indeed, aberrant TLR4 and TLR5 activations are etiologically associated with the development and progress of intestinal inflammatory diseases including inflammatory bowel disease and necrotizing enterocolitis. In this review article, we present the molecular mechanism by which TLRs elicit intracellular signal transduction, and summarize the physiological relevance of TLRs related to the gastrointestinal tract.
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DOI：
10.1073/pnas.0605200103
发表时间：
2006-08-15
影响因子：
11.1
作者：
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通讯作者：
Alexopoulou, Lena
影响因子：
2.9
作者：
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Madara, JL
影响因子：
3.1
作者：
Ewaschuk, Julia B.;Backer, Jody L.;Madsen, Karen L.
通讯作者：
Madsen, Karen L.
影响因子：
4.8
作者：
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通讯作者：
Rhee, Sang Hoon