Eosinophil-mediated suppression and Anti-IL-5 enhancement of plasmacytoid dendritic cell interferon responses in asthma

Blood plasmacytoid dendritic cells (pDCs) purified from anonymous donors were stimulated?ex vivo?with rhinovirus-16 (RV) in the presence or absence of eosinophil supernatants. Purified pDCs from 8 individuals with moderate-severe asthma, treated or not treated with anti-IL-5/5Ra therapy, were cultured with or without RV. Transcriptome analysis revealed global repression of pDC IFN response patterns by eosinophils, most notably in basal expression of interferon stimulated genes (ISGs). Increased RV-induced IFNa secretion and transcription as well as increased basal ISG expression was detected in pDCs from participants treated with anti-IL-5/5Ra therapy. Our findings highlight a novel mechanism through which T2 inflammation regulates pDC IFNa responses relevant to RV respiratory infections in the context of eosinophilic airway disease and suggest one potential mechanism through with eosinophil-depleting therapies may reduce the severity of RV illness. Overall design: pDC virus-stimulated gene expression responses to eosinophils ex vivo or eosinophil-depleting Anti-IL-5 therapy in vivo