Martínez Isidoro, Oliveros Juan C, Cuesta Isabel, de la Barrera Jorge, Ausina Vicente, Casals Cristina, de Lorenzo Alba, García Ernesto, García-Fojeda Belén, Garmendia Junkal, González-Nicolau Mar, Lacoma Alicia, Menéndez Margarita, Moranta David, Nieto Amelia, Ortín Juan, Pérez-González Alicia, Prat Cristina, Ramos-Sevillano Elisa, Regueiro Verónica, Rodriguez-Frandsen Ariel, Solís Dolores, Yuste José, Bengoechea José A, Melero José A
Centro Nacional de Microbiología, Instituto de Salud Carlos IIIMadrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos IIIMadrid, Spain.
Centro Nacional de Biotecnología (CSIC) Madrid, Spain.
Front Microbiol. 2017 Mar 1;8:276. doi: 10.3389/fmicb.2017.00276. eCollection 2017.
Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (, and ) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here.
下呼吸道感染是人类死亡的五大主要原因之一。因此，对抗这些感染是全球卫生工作的重点。寻找几种相关呼吸道病原体共有的宿主基因表达诱导变化，是识别新型广谱宿主导向治疗靶点的一种替代方法。为此，肺泡巨噬细胞分别感染了三种不相关的细菌（、和）和两种不同的病毒（呼吸道合胞病毒和甲型流感病毒）呼吸道病原体，所有这些病原体都与人类健康高度相关。细胞还用细菌脂多糖（LPS）作为典型的病原体相关分子模式进行激活。通过微阵列分析寻找所示病原体共有的差异表达细胞基因模式。大多数共同上调的宿主基因与先天免疫反应和/或细胞凋亡有关，Toll样、RIG-I样和NOD样受体位于基因过表达的前10条信号通路中。这些结果确定了对抗此处研究的细菌和病毒引起的重要人类感染的新潜在广谱靶点。
