Plasmacytoid Dendritic Cell-Derived IFNα Modulates Th17 Differentiation During Bordetella pertussis Infection in Mice

Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). Recent studies have revealed a central role for Th17 cells in the resolution of the infection. Emerging studies document that type I interferons (IFN) suppress Th17 differentiation and IL-17 responses in models of infection and chronic inflammation. Plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs. Therefore, we hypothesize that during B. pertussis infection in mice, pDC derived IFNa inhibits a rapid increase in Th17 cells. We found that IFNa-secreting pDCs emerge in the lungs in the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection (dpi) or later. The presence of IFNa led to ablation of Th17 differentiation and proliferation in vitro. Furthermore, blocking IFNa produced by pDCs, in vivo prior to B. pertussis infection resulted in increase of Th17 frequency, inflammation and reduced bacterial loads in the airways of infected mice. Altogether, this work provides evidence of an inhibitory role for pDCs and pDC-derived IFNa in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.