Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses1

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses1
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Toll 样受体 1 在抗细菌反应中的辅助蛋白功能的证据1

DOI:
10.4049/jimmunol.165.12.7125
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发表时间:
2000
期刊:
The Journal of Immunology
影响因子:
--
通讯作者:
S. Dower
S. Dower
中科院分区:
--
文献类型:
--
作者:
D. Wyllie;E. Kiss;A. Visintin;S. C. Smith;S. Boussouf;D. Segal;G. Duff;S. Dower

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Toll样受体(TLR)家族的成员是哺乳动物抗微生物应答的组分,与IL-1受体的结构域密切相关的结构域进行信号传导。在这份报告中,TLR 1的表达和功能,一个TLR的未知功能,检查。TLR 1由单核细胞表达,如使用新型mAb所证明的。单核细胞也表达TLR 2。HeLa细胞既不表达TLR 1也不表达TLR 2,TLR 1转染不足以赋予对几种微生物提取物的响应性。然而,TLR 1和TLR 2的共转染导致HeLa细胞对脑膜炎奈瑟氏球菌释放的可溶性因子的信号传导相对于单独使用TLR的响应增强。这种现象也见于高浓度的某些LPS制剂。了N. TLR 1/TLR 2识别的脑膜炎因子不被N.脑膜炎病毒LpxA基因突变。虽然LPS生物合成需要LpxA,但由于在所有LPS制剂中均未观察到TLR 1和TLR 2之间的合作,因此TLR 1/2识别的微生物组分可能是LPS和其他分子的复合物或与LPS代谢和化学相关的化合物。功能性IL-1 R由异源二聚体组成;该报告表明,对于某些激动剂,TLR 1和TLR 2具有类似的机制。这些数据进一步表明,哺乳动物对某些细菌产物的反应可能是由TLR的组合介导的,这表明了Toll介导的反应库多样化的机制。
Members of the Toll-like receptor (TLR) family are components of the mammalian anti-microbial response, signaling with a domain closely related to that of IL-1 receptors. In this report the expression and function of TLR1, a TLR of unknown function, are examined. TLR1 is expressed by monocytes, as demonstrated using a novel mAb. Monocytes also express TLR2. TLR1 transfection of HeLa cells, which express neither TLR1 nor TLR2, was not sufficient to confer responsiveness to several microbial extracts. However, cotransfection of TLR1 and TLR2 resulted in enhanced signaling by HeLa cells to soluble factors released from Neisseria meningitidis relative to the response with either TLR alone. This phenomenon was also seen with high concentrations of some preparations of LPS. The N. meningitidis factors recognized by TLR1/TLR2 were not released by N. meningitidis mutant in the LpxA gene. Although LpxA is required for LPS biosynthesis, because cooperation between TLR1 and TLR2 was not seen with all LPS preparations, the microbial component(s) TLR1/2 recognizes is likely to be a complex of LPS and other molecules or a compound metabolically and chemically related to LPS. The functional IL-1R consists of a heterodimer; this report suggests a similar mechanism for TLR1 and TLR2, for certain agonists. These data further suggest that mammalian responsiveness to some bacterial products may be mediated by combinations of TLRs, suggesting a mechanism for diversifying the repertoire of Toll-mediated responses.
DOI: 10.4049/jimmunol.163.1.1
发表时间: 1999-07
影响因子: 4.4
作者:
A. Yoshimura;E. Lien;R. Ingalls;E. Tuomanen;R. Dziarski;D. Golenbock
通讯作者: A. Yoshimura;E. Lien;R. Ingalls;E. Tuomanen;R. Dziarski;D. Golenbock
DOI: 10.1126/science.285.5428.736
发表时间: 1999-07-30
期刊: SCIENCE
影响因子: 56.9
作者:
Aliprantis, AO;Yang, RB;Zychlinsky, A
通讯作者: Zychlinsky, A