TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes.
TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes.
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TLR1/TLR2异二聚体在识别伯氏螺旋体中起着重要作用。
DOI：
10.1371/journal.pone.0025998
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Joosten LA
中科院分区：
文献类型：
--
作者：
Oosting M;Ter Hofstede H;Sturm P;Adema GJ;Kullberg BJ;van der Meer JW;Netea MG;Joosten LA
感染疏螺旋体后，患莱姆病的风险因人而异。免疫系统对疏螺旋体的识别是由模式识别受体(PRRs)介导的，如TLRs。虽然TLR2是疏螺旋体的主要识别受体，但对TLR1和TLR6的作用知之甚少，它们都能与TLR2形成具有功能活性的异源二聚体。在这里，我们研究了小鼠和人TLR1和TLR6对疏螺旋体的识别。分离TLR1和TLR6基因缺陷小鼠的腹腔巨噬细胞，并与疏螺旋体接触。用疏螺旋体刺激人外周血单核细胞，用特异性抗体阻断或不阻断TLR1和TLR6。最后，我们评估了TLR基因多态性对疏螺旋体诱导的细胞因子产生的功能影响。分离的−/−和−/−小鼠脾细胞经伯氏杆菌刺激后，Th1/Th2细胞因子失衡，而促炎细胞因子的产生无明显差异。相反，用特异性中和抗体阻断TLR1导致暴露于伯氏杆菌后的人PBMCs产生的细胞因子减少。阻断人TLR6并不能抑制细胞因子的产生。当携带TLR1基因多态性的健康个体的PBMC暴露于伯氏杆菌后，与野生型对照相比，体外细胞因子的产生显著减少。TLR6基因多态导致少量修饰细胞因子的产生。这项研究表明，TLR1/TLR2异源二聚体在诱导螺旋体在人体早期炎症反应中起主导作用。
After infection with Borrelia species, the risk for developing Lyme disease varies significantly between individuals. Recognition of Borrelia by the immune system is mediated by pattern recognition receptors (PRRs), such as TLRs. While TLR2 is the main recognition receptor for Borrelia spp., little is known about the role of TLR1 and TLR6, which both can form functionally active heterodimers with TLR2. Here we investigated the recognition of Borrelia by both murine and human TLR1 and TLR6. Peritoneal macrophages from TLR1- and TLR6- gene deficient mice were isolated and exposed to Borrelia. Human PBMCs were stimulated with Borrelia with or without specific TLR1 and TLR6 blocking using specific antibodies. Finally, the functional consequences of TLR polymorphisms on Borrelia-induced cytokine production were assessed. Splenocytes isolated from both TLR1−/− and TLR6−/− mice displayed a distorted Th1/Th2 cytokine balance after stimulation with B.burgdorferi, while no differences in pro-inflammatory cytokine production were observed. In contrast, blockade of TLR1 with specific neutralizing antibodies led to decreased cytokine production by human PBMCs after exposure to B.burgdorferi. Blockade of human TLR6 did not lead to suppression of cytokine production. When PBMCs from healthy individuals bearing polymorphisms in TLR1 were exposed to B.burgdorferi, a remarkably decreased in vitro cytokine production was observed in comparison to wild-type controls. TLR6 polymorphisms lead to a minor modified cytokine production. This study indicates a dominant role for TLR1/TLR2 heterodimers in the induction of the early inflammatory response by Borrelia spirochetes in humans.
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影响因子：
15.9
作者：
Netea, MG;Demacker, PNM;vanderMeer, JWM
通讯作者：
vanderMeer, JWM
影响因子：
4.4
作者：
Johnson, Christopher M.;Lyle, Elizabeth A.;Tapping, Richard I.
通讯作者：
Tapping, Richard I.
影响因子：
--
作者：
Netea, Mihai G.;van de Veerdonk, Frank;Kullberg, Bart Jan
通讯作者：
Kullberg, Bart Jan
DOI：
10.1083/jcb.200304093
发表时间：
2003-09-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sandor F;Latz E;Re F;Mandell L;Repik G;Golenbock DT;Espevik T;Kurt-Jones EA;Finberg RW
通讯作者：
Finberg RW
DOI：
10.1196/annals.1358.012
发表时间：
2005-01-01
期刊：
HUMAN IMMUNOLOGY: PATIENT-BASED RESEARCH
影响因子：
--
作者：
Kesh, S;Mensah, NY;Papanicolaou, GA
通讯作者：
Papanicolaou, GA