Microbial lipopeptides stimulate dendritic cell maturation via toll-like receptor 2
Microbial lipopeptides stimulate dendritic cell maturation via toll-like receptor 2
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DOI：
10.4049/jimmunol.166.4.2444
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Modlin, RL
中科院分区：
文献类型：
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作者：
Hertz, CJ;Kiertscher, SM;Modlin, RL
树突状细胞（DC）在初始T细胞中启动免疫应答的能力取决于成熟过程，该成熟过程允许细胞发展其有效的Ag呈递能力。虽然未成熟DC可以通过用GM-CSF和IL-4处理外周血单核细胞在体外衍生，但是需要额外的信号，例如由TNF-α、CD 40配体或LPS提供的信号，以实现完全成熟和最大APC功能。由于我们最近发现微生物脂蛋白可以通过Tall样受体（TLR）2激活单核细胞和DC，我们还研究了脂蛋白是否可以驱动DC成熟。未成熟DC在有或没有脂蛋白的情况下培养，并监测指示成熟的细胞表面标志物的表达。用脂肽刺激增加了CD 83、II类MHC、CD 80、CD 86、CD 54和CD 58的表达，并降低了CD 32的表达和内吞活性;这些脂肽成熟的DC还显示出在MLR中增强的T细胞刺激能力，如通过T细胞增殖和IFN-γ分泌所测量的。发现脂肽的脂质部分对于诱导成熟是必需的。在加入脂肽之前，将成熟DC与抗TLR 2阻断抗体预孵育，阻断了与DC成熟相关的表型和功能变化。这些结果表明，脂肽可以通过TLR 2刺激DC成熟，提供了一种细菌产物可以参与免疫应答启动的机制。免疫学杂志，2001，166：2413-2450.
The ability of dendritic cells (DC) to initiate immune responses in naive T cells is dependent upon a maturation process that allows the cells to develop their potent Ag-presenting capacity. Although immature DC can be derived in vitro by treatment of peripheral blood monocytes with GM-CSF and IL-4, additional signals such as those provided by TNF-alpha, CD40 ligand, or LPS are required for complete maturation and maximum APC function. Because we recently found that microbial lipoproteins can activate monocytes and DC through Tall-like receptor (TLR) 2, we also investigated whether lipoproteins can drive DC maturation. Immature DC were cultured with or without lipoproteins and were monitored for expression of cell surface markers indicative of maturation. Stimulation with lipopeptides increased expression of CD83, MHC class II, CD80, CD86, CD54, and CD58, and decreased CD32 expression and endocytic activity; these lipopeptide-matured DC also displayed enhanced T cell stimulatory capacity in MLR, as measured by T cell proliferation and IFN-gamma secretion, The lipid moiety of the lipopeptide was found to be essential for induction of maturation. Preincubation of maturing DC with an anti-TLR2 blocking Ab before addition of lipopeptide blocked the phenotypic and functional changes associated with DC maturation. These results demonstrate that lipopeptides can stimulate DC maturation via TLR2, providing a mechanism by which products of bacteria can participate in the initiation of an immune response. The Journal of Immunology, 2001, 166: 2413-2450.