High-mobility group box-1 protein from CC10+ club cells promotes type 2 response in the later stage of respiratory syncytial virus infection

Abstract

The type 2 immune response, induced by infection of respiratory syncytial virus (RSV), has been linked to asthma development, but it remains unclear how the response is initiated. Here, we reported that the high-mobility group box-1 (HMGB1) protein promotes the type 2 response in the later stage of RSV infection. In mice, we found that type 2 cytokines were elevated in the later stages, which were strongly diminished after administration of anti-HMGB1 antibodies. Further investigation revealed that HMGB1 expression was localized to CC10+ club cells in the lung. In the clinic, levels of HMGB1 in nasopharyngeal aspirates in hospitalized infants with RSV bronchiolitis [median (interquartile range) 161.20 ng/ml (68.06–221.30)] were significantly higher than those without lower respiratory tract infections [21.94 ng/ml (12.12–59.82); P < 0.001]. Moreover, higher levels of HMGB1 correlated with clinical severity. These results reveal a link between viral infection and the asthma-like type 2 responses that are associated with long-term consequences.