BioProject

Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have historically focused on antibiotic development and vaccine-enhanced adaptive immunity. More...

Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have historically focused on antibiotic development and vaccine-enhanced adaptive immunity. However, we have recently reported that the lungs’ innate defenses can be therapeutically induced by inhalation of a combination of synthetic TLR ligands that synergize to protect mice against otherwise lethal pneumonia. Simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent Gram-positive and Gram-negative pathogens, as well as viruses. Protection is associated with rapid pathogen killing in the lungs, and pathogen killing can be induced from lung epithelial cells in isolation. Here we explore the mechanisms underlying this dramatic phenomenon by performing microarray gene expression analysis of mouse lungs treated by aerosol with PBS (sham treatment), Pam2CSK4 (TLR 2/6 ligand), ODN2395 (TLR9 ligand), or both TLR ligands. Overall design: C57BL/6J mice were placed, unrestrained, in a aerosolization chamber and inhalationally exposed to 20 minute treatment with an 8 ml volume of PBS (sham), Pam2CSK4 10 ug/ml, ODN 2395 20 ug/ml, or the combination. 4 h after treatment, the mice were deeply anesthetized, their lungs were harvested, homogenized, and total RNA was extracted. Amplified cRNA was hybridized to Illumina Sentrix MouseRef-8 v2 Beadhips, labeled with Cy3, and scanned on an Illumina iScan. At least 8 unique samples were obtained per condition. Less...