Microbes mediated host innate immune response in idiopathic pulmonary fibrosis

Background: The host immune response to lung microbes in idiopathic pulmonary fibrosis (IPF) is unclear. Objective: Investigate immune pathways implicated by presence of operational taxonomic units (OTU) microbiota from bronchoscopy IPF lung samples, and if bacterial CpG-oligodeoxynucleotide (CpG-ODN) motifs mediated fibroblast TLR9 activation is involved. Methods: Paired gene expression arrays and 16S rDNA sequencing data of 68 IPF patients were retrieved from COMET study. R package “WGCNA” were used to construct gene co-expression modules. Each eigengene value was correlated with each trait. Results: Figure 1 showed 10 modules and their respective positive/negative correlation with each trait. Magenta module significantly correlated with the D L CO ( p =0.007), species richness ( p =5x10 -6 ), and OTU1302 ( Pseudomonas ) ( p =0.0001). Purple module correlated OTU1341 ( Prevotella ) ( p =0.003) and OTU1348 ( Staphylococcus ) ( p =0.03) and negatively correlated with CpG response ( p =0.03). D L CO and CpG response significantly correlated with blue module with opposite directions. Canonical pathways enriched in magenta, purple, and blue modules are integrin signaling, regulation of epithelial-mesenchymal transition, and Toll-like receptor signaling, respectively. CONCLUSIONS: The integrated analysis of host transcriptome with lung microbiota and CpG-ODN response unveiled underlying molecular mechanism of microbes mediated host innate immune response in IPF.