Contrasting gene expression patterns associated with high and low rhinovirus stimulated IFN-α production

Introduction: Viral respiratory infections cause considerable morbidity and economic loss. While rhinoviruses (RV) typically cause little more than the common cold, they can produce severe infections and disease exacerbations in susceptible individuals, including those with chronic lung diseases. Variations in the regulation of key antiviral cytokines, particularly type I interferon (IFN-α and IFN-b), may contribute to RV susceptibility, but are not well understood. Method: Whole genome transcription patterns were assessed in samples from 74 individuals demonstrating high or low IFN-α production following RV stimulation in vitro. Results: In unstimulated samples (baseline) the high IFN-α producer group showed higher expression of genes associated with plasmacytoid dendritic cells, the complement system, B-cell chemokines, immune regulation, macrophages, and vitamin D activation and lower expression of genes linked to haemoglobin and haem biosynthesis, wound healing, stress response and pro-inflammatory genes than the low IFN-α producer group. After RV stimulation, the high IFN-α producer group showed more intense upregulation of diverse immune function genes including IFNs and greater downregulation of genes linked to structural and extra-cellular matrix functions than the low IFN-α producer group. Patterns of antibacterial gene expression varied between groups. Healthy people and those with asthma generally showed similar gene expression patterns. These findings highlight multiple biological pathways whose expression patterns differ substantially between high and low IFN-α producers. These differences likely contribute to variations in anti-RV immunity and immunopathology between individuals. Differentially expressed genes between high and low IFN-α producing PBMC