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首页> 外文期刊>BMC Infectious Diseases >Gene expression profiling of human alveolar macrophages infected by B. anthracis spores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogen
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Gene expression profiling of human alveolar macrophages infected by B. anthracis spores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogen

机译：炭疽芽孢杆菌孢子感染人肺泡巨噬细胞的基因表达谱表明TNF-α和NF-κb是对病原体先天免疫反应的关键成分

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Background Bacillus anthracis, the etiologic agent of anthrax, has recently been used as an agent of bioterrorism. The innate immune system initially appears to contain the pathogen at the site of entry. Because the human alveolar macrophage (HAM) plays a key role in lung innate immune responses, studying the HAM response to B. anthracis is important in understanding the pathogenesis of the pulmonary form of this disease. Methods In this paper, the transcriptional profile of B. anthracis spore-treated HAM was compared with that of mock-infected cells, and differentially expressed genes were identified by Affymetrix microarray analysis. A portion of the results were verified by Luminex protein analysis. Results The majority of genes modulated by spores were upregulated, and a lesser number were downregulated. The differentially expressed genes were subjected to Ingenuity Pathway analysis, the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, the Promoter Analysis and Interaction Network Toolset (PAINT) and Oncomine analysis. Among the upregulated genes, we identified a group of chemokine ligand, apoptosis, and, interestingly, keratin filament genes. Central hubs regulating the activated genes were TNF-α, NF-κB and their ligands/receptors. In addition to TNF-α, a broad range of cytokines was induced, and this was confirmed at the level of translation by Luminex multiplex protein analysis. PAINT analysis revealed that many of the genes affected by spores contain the binding site for c-Rel, a member of the NF-κB family of transcription factors. Other transcription regulatory elements contained in many of the upregulated genes were c-Myb, CP2, Barbie Box, E2F and CRE-BP1. However, many of the genes are poorly annotated, indicating that they represent novel functions. Four of the genes most highly regulated by spores have only previously been associated with head and neck and lung carcinomas. Conclusion The results demonstrate not only that TNF-α and NF-κb are key components of the innate immune response to the pathogen, but also that a large part of the mechanisms by which the alveolar macrophage responds to B. anthracis are still unknown as many of the genes involved are poorly annotated.
机译：背景技术炭疽杆菌是炭疽病的病原体，最近已被用作生物恐怖主义的媒介。先天免疫系统最初似乎在进入位点包含病原体。由于人肺泡巨噬细胞（HAM）在肺部先天免疫反应中起关键作用，因此研究对炭疽芽孢杆菌的HAM反应对于了解这种疾病的肺部形式的发病机理很重要。方法将炭疽芽孢杆菌孢子处理过的HAM与模拟感染细胞的转录谱进行比较，并通过Affymetrix微阵列分析鉴定差异表达的基因。通过Luminex蛋白分析验证了部分结果。结果孢子调控的大多数基因被上调，而较少的被下调。对差异表达的基因进行了独创性途径分析，注释，可视化和综合发现数据库（DAVID）分析，启动子分析和相互作用网络工具集（PAINT）和Oncomine分析。在上调的基因中，我们鉴定了一组趋化因子配体，凋亡和有趣的是角蛋白丝基因。调节激活基因的中心枢纽是TNF-α，NF-κB及其配体/受体。除TNF-α外，还诱导了广泛的细胞因子，并通过Luminex多重蛋白分析在翻译水平上证实了这一点。 PAINT分析显示，许多受孢子影响的基因均含有c-Rel（转录因子NF-κB家族成员）的结合位点。许多上调基因中包含的其他转录调控元件是c-Myb，CP2，Barbie Box，E2F和CRE-BP1。但是，许多基因的注释不充分，表明它们代表了新颖的功能。孢子高度调控的四个基因以前仅与头颈部和肺癌有关。结论结果表明，不仅TNF-α和NF-κb是病原体固有免疫反应的关键成分，而且肺泡巨噬细胞对炭疽芽孢杆菌的反应机制的大部分仍不为人所知。涉及的基因注释不善。

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