Qu Xueqi, Cinar Mehmet U, Fan Huitao, Pröll Maren, Tesfaye Dawit, Tholen Ernst, Looft Christian, Hölker Michael, Schellander Karl, Uddin Muhammad J
Institute of Animal Science, University of Bonn, Bonn, Germany.
Institute of Animal Science, University of Bonn, Bonn, Germany Department of Animal Science, Faculty of Agriculture, Erciyes University, Kayseri, Turkey.
Innate Immun. 2015 Apr;21(3):242-54. doi: 10.1177/1753425914526266. Epub 2014 Mar 19.
Dendritic cell (DC) subsets form a remarkable cellular network that regulate innate and adaptive immune responses. Although pigs are the most approximate model to humans, little is known about the regulation of monocyte-derived DCs (moDCs) and splenic DCs (SDCs) in the initiation of immune responses under inflammatory conditions. We investigated the activation and maturation of porcine moDC and SDC subpopulations following LPS stimulation. Porcine monocytes that would differentiate into moDCs were isolated. SDCs were isolated directly from the porcine spleen. Following LPS stimulation, phagocytosis activity, TLR4/MyD88-dependent gene expression, co-stimulatory molecule, and pro-inflammatory cytokine (TNF-α, IL-1β) and chemokine (IL-8) expressions were increased in both cell subsets. Furthermore, moDCs showed higher levels of gene and protein expression compared with SDCs. Interestingly, moDCs were found to be more responsive via the TLR4/TRAF-dependent signalling pathway of activation. Only SDCs expressed higher level of IL-12p40 gene and protein, whereas, IFN-γ gene and protein expression were likely to be unchanged after LPS stimulation in both cell subtypes. These data demonstrate that porcine moDCs display a greater ability to initiate innate immune responses, and could be used as a model to investigate immune responses against Ags.
树突状细胞(DC)亚群构成了一个卓越的细胞网络,可调节先天性和适应性免疫反应。尽管猪是与人类最接近的模型,但在炎症条件下免疫反应启动过程中,关于单核细胞衍生的DC(moDC)和脾DC(SDC)的调节机制却知之甚少。我们研究了脂多糖(LPS)刺激后猪moDC和SDC亚群的激活与成熟情况。分离出了将分化为moDC的猪单核细胞。直接从猪脾脏中分离出SDC。LPS刺激后,两个细胞亚群的吞噬活性、TLR4/MyD88依赖性基因表达、共刺激分子以及促炎细胞因子(TNF-α、IL-1β)和趋化因子(IL-8)表达均增加。此外,与SDC相比,moDC显示出更高水平的基因和蛋白表达。有趣的是,发现moDC通过TLR4/TRAF依赖性激活信号通路反应更强。只有SDC表达更高水平的IL-12p40基因和蛋白,而在LPS刺激后,两种细胞亚型中的IFN-γ基因和蛋白表达可能未发生变化。这些数据表明,猪moDC在启动先天性免疫反应方面表现出更强的能力,可作为研究针对抗原的免疫反应的模型。