标题： 从分泌组分析到免疫学：壳聚糖通过依赖于TLR4的机制诱导树突状细胞活化的重大变化 显示英文标题

标题： From secretome analysis to immunology: chitosan induces major alterations in the activation of dendritic cells via a TLR4-dependent mechanism

摘要： 树突状细胞已知可被广泛的微生物产物激活，导致细胞因子的产生和膜标记物（如主要组织相容性复合体II类分子）水平的增加。 这种激活的树突状细胞具有激活初始T细胞的能力。 在本研究中，我们证明未成熟树突状细胞分泌YM1凝集素和脂ocalin-2。 通过检测这两种蛋白的配体，分别是壳聚糖和铁载体，我们也证明壳聚糖是一种各种真菌和原生动物细胞壁的降解产物，通过TLR4依赖的机制，以膜蛋白如II类分子、CD80和CD86的上调为标志，在膜水平上诱导树突状细胞的激活，但不能诱导细胞因子的产生。 这导致产生了无法刺激T细胞的激活树突状细胞。 然而，与其他微生物产物共同刺激克服了这种部分激活，并恢复了这些激活的树突状细胞刺激T细胞的能力。 此外，连续用壳聚糖然后用脂多糖刺激，诱导了树突状细胞产生的IL-12/IL-10平衡的剂量依赖性变化。 显示英文摘要

摘要： Dendritic cells are known to be activated by a wide range of microbial products, leading to cytokine production and increased levels of membrane markers such as major histocompatibility complex class II molecules. Such activated dendritic cells possess the capacity to activate na\"ive T cells. In the present study we demonstrated that immature dendritic cells secrete both the YM1 lectin and lipocalin-2. By testing the ligands of these two proteins, chitosan and siderophores, respectively, we also demonstrated that chitosan, a degradation product of various fungal and protozoal cell walls, induces an activation of dendritic cells at the membrane level, as shown by the up-regulation of membrane proteins such as class II molecules, CD80 and CD86 via a TLR4-dependent mechanism, but is not able to induce cytokine production. This led to the production of activated dendritic cells unable to stimulate T cells. However, costimulation with other microbial products overcame this partial activation and restored the capacity of these activated dendritic cells to stimulate T cells. In addition, successive stimulation with chitosan and then by lipopolysaccharide induced a dose-dependent change in the cytokinic IL-12/IL-10 balance produced by the dendritic cells.