Transcriptional control in the macrophage response to pathogens

巨噬细胞是指导对病原体的先天免疫反应的关键细胞， 特定的模式识别受体我们将分析巨噬细胞的转录组， 类鼻疽伯克霍尔德氏菌和确定转录因子和信号分子， 以应对感染。通过检查缺乏中枢信号分子的巨噬细胞，我们将 将特定的转录簇归因于TLR信号传导（MyD 88/Trif无效细胞）、NLR信号传导（Rip 2或Rip 3）、NLR信号传导（MyD 88/Trif无效细胞）、NLR信号传导（MyD 88/Trif无效细胞）、NLR信号传导（MyD 88/Trif无效细胞）、NLR信号传导（MyD 88/Trif无效细胞）和NLR信号传导（MyD 88/Trif无效细胞）。 半胱天冬酶1无效细胞）或I型干扰素信号传导（IFNaRI无效细胞）。同时，我们将确定 在B中对特异性细菌毒力因子或PAMP的转录应答。假鼻疽，包括 III型和VI型分泌系统、肌动蛋白聚合、鞭毛蛋白和群体感应。我们将 通过计算确定被激活的特定转录因子，并确定基因纲要 三个转录因子中的每一个都在调节。最后，我们将验证转录网络， 定义并确定它们对B的影响。体内和体外的类鼻疽感染。

Macrophages are key cells that direct innate immune responses to pathogens that are detected through specific pattern recognition receptors. We will analyze the transcriptomes of macrophages infected with Burkholderia pseudomallei and determine the transcription factors and signaling molecules that are activated in response to infection. By examining macrophages deficient for central signaling molecules, we will ascribe specific transcriptional clusters to TLR signaling (MyD88/Trif null cells), NLR signaling (Rip2 or caspase 1 null cells) or type I interferon signaling (IFNaRI null cells). In parallel, we will determine the transcriptional response to specific bacterial virulence factors or PAMPs in B. pseudomallei, including the type III and VI secretion systems, actin polymerization, flagellin and quorum sensing. We will computationally identify specific transcription factors that are activated and identify the compendium of genes that each of three transcription factor regulates. Finally, we will validate the transcriptional networks that are defined and determine their effect on B. pseudomallei infection in vivo and in vitro.