Tross Debra, Petrenko Lev, Klaschik Sven, Zhu Qing, Klinman Dennis M
Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, United States.
Mol Immunol. 2009 Aug;46(13):2557-64. doi: 10.1016/j.molimm.2009.05.011. Epub 2009 Jun 16.
The innate immune system is triggered when pathogen-associated molecular patterns (PAMPs) expressed by infectious microorganisms interact with toll-like receptors (TLR) present on immune cells. Individual TLRs signal through distinct molecular pathways. For example, TLR9 interacts with unmethylated CpG motifs expressed by bacterial DNA and triggers via a MyD88 dependent pathway whereas TLR3 recognizes viral RNA through a MyD88-independent pathway. Bioinformatic analysis of microarray data was used to identify the regulatory patterns underlying changes in gene expression induced when RAW 264.7 macrophages were stimulated via TLR9 by CpG oligonucleotides (ODN) and/or via TLR3 by poly (I:C). While the genes activated by each ligand mediated similar functions, poly (I:C) elicited a larger and more diverse change in gene expression. Co-stimulation with both ligands accelerated gene expression and synergistically activated genes primarily associated with immune function. This is the first work to compare global changes in gene regulation triggered by distinct TLR pathways and clarify their impact on gene expression.
当感染性微生物表达的病原体相关分子模式（PAMP）与免疫细胞上存在的Toll样受体（TLR）相互作用时，固有免疫系统被触发。单个TLR通过不同的分子途径发出信号。例如，TLR9与细菌DNA表达的未甲基化CpG基序相互作用，并通过MyD88依赖性途径触发，而TLR3通过MyD88非依赖性途径识别病毒RNA。利用微阵列数据的生物信息学分析来确定当RAW 264.7巨噬细胞通过CpG寡核苷酸（ODN）经TLR9和/或通过聚肌苷酸胞苷酸（poly (I:C)）经TLR3刺激时基因表达变化背后的调控模式。虽然每种配体激活的基因介导相似的功能，但poly (I:C)引起的基因表达变化更大且更多样化。两种配体共同刺激加速了基因表达，并协同激活了主要与免疫功能相关的基因。这是第一项比较由不同TLR途径触发的基因调控全局变化并阐明其对基因表达影响的研究。
