Transcriptional response to RSV in asthma primary bronchial epithelial cells: are the basal cells responsible for the reduced NF-kB response?

Rationale: Respiratory syncytial virus (RSV) infection can cause asthma exacerbations. Most - but not all - studies showed that the type-I interferon dependent antiviral response induced by the epithelial cells after RSV infection is reduced in asthma. The molecular mechanisms responsible for the impaired response in asthmatic bronchial epithelium remain unknown. Here, we aimed to characterize the transcriptional response of primary bronchial epithelial cells (PBECs) to RSV infection in asthma. Methods: Results: PBECs from asthma patients displayed a reduction in ciliated cell proportions and barrier function. Gene set enrichment analyses revealed an enhanced pro-inflammatory response to RSV in healthy PBECs. Initial sc-RNAseq analysis (n=4 per group) revealed presence of a strong NF-kB response from basal and secretory epithelial cells, which was reduced in asthma PBECs. Cell type deconvolution revealed an increase in proportion of ciliated cells (p=0,023) and a decrease in basal cells (p=0,047) after RSV infection in asthma. Additional scRNA-seq data (n=8 per group in total) will reveal whether ciliated cell responses to RSV are altered in asthma. Conclusion: Our results highlight that the response to RSV infection is altered in the bronchial epithelium in asthma, with a reduced inflammatory response and a shift in cell-type composition after viral infection.