Theiner Gabi, Rössner Susanne, Dalpke Alexander, Bode Konrad, Berger Thomas, Gessner André, Lutz Manfred B
Department of Dermatology, University Hospital Erlangen, Germany.
Mol Immunol. 2008 Jan;45(1):244-52. doi: 10.1016/j.molimm.2007.02.021. Epub 2007 Jun 27.
Toll-like receptors (TLR) are expressed on the surface or intracellularly by dendritic cells (DC) and recognize specifically different pathogen-associated molecular patterns (PAMPs). Increasing evidence suggests that TLR expressed by DC can cooperate to synergize their functions. Here, we describe the cooperation of TLR9 and TLR4 triggering of murine bone marrow derived DC by CpG oligonucleotides and LPS, respectively. The simultaneous DC stimulation of LPS and CpG showed additive effects on the production of IL-12 but not on other cytokines, such as TNF, IL-6 or IL-10. CpG pretreatment before LPS induced five times more IL-12p40 and IL-12p70 production by DC, whereas LPS pretreatment before CpG showed no effect. The optimal time interval between CpG and LPS treatment was 4h and the synergistic effects were dependent on myeloid differentiation factor 88 (MyD88) but independent from the DNA backbone and did not mediate by nucleosome remodeling. The stimulatory effect could be further enhanced by addition of IFN-gamma but not anti-CD40 antibodies. These data show, that TLR4 and TLR9 can cooperate to increase selectively IL-12 production by DC.
Toll样受体（TLR）由树突状细胞（DC）在表面或细胞内表达，并特异性识别不同的病原体相关分子模式（PAMP）。越来越多的证据表明，DC表达的TLR可以协同发挥其功能。在此，我们描述了分别由CpG寡核苷酸和脂多糖（LPS）触发的TLR9和TLR4对小鼠骨髓来源DC的协同作用。LPS和CpG同时刺激DC对IL-12的产生具有累加效应，但对其他细胞因子，如TNF、IL-6或IL-10则没有影响。LPS之前进行CpG预处理可使DC产生的IL-12p40和IL-12p70增加五倍，而CpG之前进行LPS预处理则无效果。CpG和LPS处理之间的最佳时间间隔为4小时，协同效应依赖于髓样分化因子88（MyD88），与DNA骨架无关，且不由核小体重塑介导。添加IFN-γ可进一步增强刺激效果，但抗CD40抗体则不能。这些数据表明，TLR4和TLR9可以协同作用，选择性地增加DC产生IL-12。
