Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Eur J Immunol. 2011 Mar;41(3):694-705. doi: 10.1002/eji.201040808. Epub 2011 Jan 18.
The appearance of group 1 CD1 proteins (CD1a, CD1b and CD1c) on maturing myeloid DC is a key event that converts myeloid DC to effective lipid APC. Here, we show that Borrelia burgdorferi, the causative agent of Lyme disease, triggers appearance of group 1 CD1 proteins at high density on the surface of human myeloid DC during infection. Within human skin, CD1b and CD1c expression was low or absent prior to infection, but increased significantly after experimental infections and in erythema migrans lesions from Lyme disease patients. The induction of CD1 was initiated by borrelial lipids acting through TLR-2 within minutes, but required 3 days for maximum effect. The delay in CD1 protein appearance involved a multi-step process whereby TLR-2 stimulated cells release soluble factors, which are sufficient to transfer the CD1-inducing effect in trans to other cells. Analysis of these soluble factors identified IL-1β as a previously unknown pathway leading to group 1 CD1 protein function. This study establishes that upregulation of group 1 CD1 proteins is an early event in B. burgdorferi infection and suggests a stepwise mechanism whereby bacterial cell walls, TLR activation and cytokine release cause DC precursors to express group 1 CD1 proteins.
簇群 1 CD1 蛋白（CD1a、CD1b 和 CD1c）在成熟髓系树突状细胞（maturation myeloid DC）上的出现是将髓系 DC 转化为有效脂质 APC 的关键事件。在这里，我们表明伯氏疏螺旋体（导致莱姆病的病原体）在感染期间可在人髓系 DC 表面以高密度触发簇群 1 CD1 蛋白的出现。在人类皮肤中，在感染之前 CD1b 和 CD1c 的表达水平较低或不存在，但在实验性感染后和莱姆病患者的游走性红斑损伤中显著增加。CD1 的诱导是由细菌脂质通过 TLR-2 在数分钟内引发的，但需要 3 天才能达到最大效果。CD1 蛋白出现的延迟涉及一个多步骤过程，其中 TLR-2 刺激细胞释放可溶性因子，这些因子足以在转染中将 CD1 诱导效应转移到其他细胞。对这些可溶性因子的分析确定 IL-1β 是一种先前未知的途径，可导致簇群 1 CD1 蛋白功能。这项研究确立了簇群 1 CD1 蛋白的上调是 B. burgdorferi 感染的早期事件，并表明了一个逐步的机制，即细菌细胞壁、TLR 激活和细胞因子释放导致 DC 前体表达簇群 1 CD1 蛋白。
