Airway and blood monocyte transcriptomic profiling reveals an antiviral phenotype in RSV-infected infants with severe disease

Abstract Background Respiratory syncytial virus (RSV) infection is the primary cause of lower respiratory tract infections in children under 5 years of age. Monocytes, especially in the respiratory tract are suggested to contribute to RSV pathology but their role is incompletely understood. With transcriptomic profiling of blood and airway monocytes, we describe the role of monocytes in severe RSV infection. Methods Tracheobronchial aspirates and blood samples were collected from both control (n=9) and RSV infected (n=14) patients admitted to the paediatric intensive care unit. Monocytes (CD14+) were sorted and analysed by RNA-sequencing for transcriptomic profiling. Results Both peripheral blood and airway monocytes of RSV patients showed an increased expression of antiviral and interferon-responsive genes compared to controls. Cytokine signalling showed a shared response between blood and airway monocytes, while also displaying responses that were more pronounced based on the tissue of origin. Airway monocytes upregulated additional genes related to migration and inflammation. Conclusions We found that the RSV-induced interferon response extends from the airways to the peripheral blood. Moreover, RSV induces a migration-promoting transcriptional program in monocytes. Unravelling the monocytic response and its role in the immune response to RSV infection could help the development of therapeutics to prevent severe disease.