3-O-C12-HSL通过阻碍人树突状细胞成熟介导Th细胞极性分化

3-O-C12-HSL promotes the induction of Th2 cell by preuenting human dendritic cells maturation

目的探讨铜绿假单胞菌分泌的信号分子3-O-C12-HSL对脂多糖诱导的人外周血单核细胞来源树突状细胞（Mo．DCs）成熟及n细胞极化的干预作用。方法采用免疫磁珠法分选人外周血CDl4＋单核细胞，经重组人粒一单核细胞集落刺激因子和重组人IL-4诱导其分化为Mo-DCs。CCK-8法检测3-0．CIrHSL对Mo．DCs活性影响；流式细胞术检测3-O-C12-HSL对Mo-DCs表型（CDlle-,CD40、CD80、HIJA．DR）的影响；ELISA检测Mo—DCs培养上清IFN-1和IL-12浓度；混合淋巴细胞反应观察3-O．C旷HSL对Th细胞增殖和细胞因子分泌的影响。结果3-O-C12-HSL终浓度200μmol／L时可影响Mo-DCs活性。与脂多糖对照组比较，终浓度50μmoL／L和100μmoL／L的3-O-C12-HSL明显下调脂多糖诱导的Mo-DCs表面分子CD40、CD80和HLA-DR分子表达水平，抑制Mo·DCs分泌IL-12，促进Mo．DCs分泌IL-10，抑制Th细胞增殖和IFN-γIL-12分泌，促进n细胞分泌IL-10。结论3-O-C12-HSL可抑制脂多糖诱导的Mo-DCs成熟，诱导Th2细胞极性分化，影响机体免疫系统对铜绿假单胞菌的清除作用。

Objective To investigate the influence of 3-O-C12-HSL, which secreted by Pseudo- monas aeruginosa, on the maturation of monocyte-derived dendritic ceils from human peripheral blood and Th cell polarization. Methods Human peripheral blood CD14＋ monocytes were separated by immunomagnetic beads and induced by human granulocyte monocyte colony stimulating factor and human intedeukin 4 in cul- ture. CCK-8 method was used to detect the influence of 3-O-C12-HSL on Mo-DCs activity. The immunophe- notypic expression of CD1 l c, CD40, CD80 and HLA-DR expression were assessed by FACS. IL-10 and IL- l2 levels in the supematant were measured by ELISA. Mixed culture of CIM T lymphocytes and Mo-DCs was used to observe the effects of 3-O-C12-HSL on the proliferation and eytokine secretion of Th cells. Results 3-O-C12-HSL affects the activity of Mo-DCs at the concentration of 200 μmol/L. 3-O-C12-HSL significantly down-regnlated the expression of cell surface molecules including CD80, CD40 and HLA-DR on Mo-DCs at the concentration of 50 μmol/L and 100 μmol/L. The secretion of IL-10 on Mo-DCs was in- creased whereas intedeukin-12 was decreased. The proliferation and IFN-γ, IL-12 secretion of Th cells were inhibited by 3-O-C22-HSL. However, IL-10 expression was enhanced. Conclusion 3-O-C12-HSL inhibited lipopolysaeeharide-induced maturation of Mo-DCs and drove Th2 cell polarization. Then, it might further affect the host immune system for clearance of Pseudomonas aeruginosa.