Abstract
<b>Rationale:</b> 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. <b>Methods:</b> <b>Results:</b> Before infection, PBECs from asthma patients displayed a reduction in ciliated cell proportions and barrier function. In gene set enrichment analyses, a pro-inflammatory response to RSV was observed in both disease groups, but this was stronger for healthy PBECs. ScRNAseq analysis 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 <b>Conclusion:</b> 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.
Published Version
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