Apoptosis, Toll-like, RIG-I-like and NOD-like receptors are pathways jointly induced by diverse respiratory bacterial and viral pathogens

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 represent an alternative to identifying new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens which are nevertheless 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 genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top ten 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. Differential gene expression analysis by Agilent microarrays. Three or more biological replicates per sample. Single-channel hybridizations (label: Cy3) to Agilent Whole Mouse Genome microarray (G4122F, Agilent Technologies, Palo Alto, CA), representing about 44,000 human genes, transcripts and controls. In all cases, comparisons are infected vs. not infected.