Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze

Background Impaired interferon response and allergic sensitisation may contribute to virus induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDC) play a key role in antiviral immunity as critical producers of type I interferons (IFN-I). pDC also express the high affinity IgE receptor (Fc?RI) through which IFN-I production may be negatively regulated. If antiviral function of pDC is associated with recurrent episodes of wheeze in young children is not well understood. This study aimed to evaluate the phenotype and function of circulating pDC in children with a longitudinally defined wheezing phenotype. Methods We performed multiparameter flow cytometry on peripheral blood mononuclear cells from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDC from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database. Results We observed a significant depletion of circulating pDC in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the IgE receptor (Fc?RI) on their pDC. Based on transcriptomic analysis, pDC from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a non-recurrent wheezing phenotype. Conclusion Our data suggests that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of Fc?RI is increased and their function as major IFN producers is impaired during acute exacerbations of wheeze. Overall design: Clinical samples obtained children with an acute respiratory wheeze, control samples were sampled from children in the community