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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling.
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Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling.

机译：TLR2与TLR1或TLR6的异二聚化可扩大配体谱，但不会导致差异信号。

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摘要

TLR are primary triggers of the innate immune system by recognizing various microorganisms through conserved pathogen-associated molecular patterns. TLR2 is the receptor for a functional recognition of bacterial lipopeptides (LP) and is up-regulated during various disorders such as chronic obstructive pulmonary disease and sepsis. This receptor is unique in its ability to form heteromers with TLR1 or TLR6 to mediate intracellular signaling. According to the fatty acid pattern as well as the assembling of the polypeptide tail, LP can signal through TLR2 in a TLR1- or TLR6-dependent manner. There are also di- and triacylated LP, which stimulate TLR1-deficient cells and TLR6-deficient cells. In this study, we investigated whether heterodimerization evolutionarily developed to broaden the ligand spectrum or to induce different immune responses. We analyzed the signal transduction pathways activated through the different TLR2 dimers using the three LP, palmitic acid (Pam)octanoic acid (Oct)(2)C-(VPGVG)(4)VPGKG, fibroblast-stimulating LP-1, and Pam(2)C-SK(4). Dominant-negative forms of signaling molecules, immunoblotting of MAPK, as well as microarray analysis indicate that all dimers use the same signaling cascade, leading to an identical pattern of gene activation. We conclude that heterodimerization of TLR2 with TLR1 or TLR6 evolutionarily developed to expand the ligand spectrum to enable the innate immune system to recognize the numerous, different structures of LP present in various pathogens. Thus, although mycoplasma and Gram-positive and Gram-negative bacteria may activate different TLR2 dimers, the development of different signal pathways in response to different LP does not seem to be of vital significance for the innate defense system.
机译：通过保守的病原体相关分子模式识别各种微生物，TLR是先天免疫系统的主要诱因。 TLR2是功能性识别细菌脂肽（LP）的受体，在各种疾病（例如慢性阻塞性肺疾病和败血症）中被上调。该受体与TLR1或TLR6形成异源体以介导细胞内信号转导的能力是独特的。根据脂肪酸模式以及多肽尾部的组装，LP可以TLR1或TLR6依赖性方式通过TLR2发出信号。也有二酰基和三酰基化的LP，它们刺激TLR1缺陷细胞和TLR6缺陷细胞。在这项研究中，我们调查了异源二聚化是否进化发展以扩大配体谱或诱导不同的免疫反应。我们分析了使用三种LP，棕榈酸（Pam）辛酸（Oct）（2）C-（VPGVG）（4）VPGKG，成纤维细胞刺激性LP-1和Pam（3）通过不同的TLR2二聚体激活的信号转导途径。 2）C-SK（4）。信号分子的显性阴性形式，MAPK的免疫印迹以及微阵列分析表明，所有二聚体均使用相同的信号级联，从而导致相同的基因激活模式。我们得出的结论是，TLR2与TLR1或TLR6的异源二聚化在进化过程中扩展了配体谱，使先天免疫系统能够识别多种病原体中存在的LP的众多不同结构。因此，尽管支原体和革兰氏阳性细菌和革兰氏阴性细菌可以激活不同的TLR2二聚体，但响应于不同LP的不同信号途径的发展对于先天防御系统似乎并不重要。

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