Type I interferons (IFN-I) promote dendritic cell death after viral infection.

Plasmacytoid dendritic cell (pDC) activation and release of IFN-I early after infection is important for mounting an effective adaptive response and curtailing viral replication. However, in the course of viral infection, pDC numbers drop precipitously.

Marco Colonna and his colleagues (J. Exp. Med. 208, 2367–2374) have now found that IFN-I itself induces pDC death. Following infection with DNA or RNA viruses, the serum concentration of IFN-I increased in parallel with a decrease in pDC numbers. As the dose of virus was increased, more IFN-I was produced, leading to a more pronounced decline in pDC numbers. The authors found that IFN-I acts directly on pDCs, activating them and inducing the expression of proapoptotic molecules, caspase activation and cell death.

Although this mechanism may be beneficial in limiting excessive pDC activation and immunopathology after viral infection, these results suggest that caution is warranted with IFN-α therapy in individuals infected with hepatitis C virus, as this IFN-I may directly reduce pDC numbers and impair antiviral responses.