Abstract
RATIONALE: The impact of Th17 lymphocytes on epithelial responses to rhinovirus infection in asthma is poorly characterized. METHODS: Bronchial epithelial cells (BECs) from children with asthma were differentiated to an organotypic epithelium and primed via co-culture with healthy donor Th17 lymphocytes for 4 days prior to apical infection with human rhinovirus-16 (RV-16). RNA sequencing with WGCNA analysis was performed to identify modules of gene expression altered by Th17 priming or RV-16 infection in BECs or Th17 cells. Gene expression was correlated with viral copy number and with secreted protein levels. RESULTS: Analysis identified 4,030 genes grouped into 9 named modules with differential gene expression in BECs due to Th17 priming and viral infection. Modules with increased expression with Th17 priming and RV-16 infection included Interferon, MAP-kinase and TNF Signaling modules, while expression of Cilia structure/function and Metabolism modules were decreased. Th17 cells co-cultured with RV-16 infected BECs exhibited increased expression of an Interferon and Viral Response Module without detectable direct viral infection of Th17 cells. Increased expression of the Interferon Signaling in BECs and Interferon Response in Th17 cells was correlated with increased viral copy number in BECs. Th17 priming of BECs led to increased secretion of IFN-α, IFN-γ, and IL-1β following RV-16 as compared to BECs alone. CONCLUSIONS: Th17 lymphocytes enhance epithelial interferon responses to RV-16 infection in bronchial epithelium from asthmatic children.