| Viral infections are often associated with a transient or long-lasting generalized suppression of the host immune response. In this study, we demonstrated that in vivo lymphocytic choriomeningitis virus (LCMV) infection in its natural rodent host resulted in a profound suppression of the unique capacity of plasmacytoid dendritic cells (pDCs) to produce Type I interferons (IFN-I). While both acute and persistent LCMV infections impaired pDC IFN-I response, only the persistent virus induced their long-lasting diversion. This immune-deficiency related to a decreased ability of the persistently infected host to mount an effective innate response to control a secondary pathogen. Importantly, the ability of pDCs to produce a variety of other cytokines, such as interleukin-6 (IL-6), was unaltered, indicating selective disruption of the IFN-I pathway. Further studies indicated that IL-6 was elevated in the serum at different times after acute versus chronic LCMV infection and it was essential for the eventual clearance of the persistent virus. Altogether, these findings demonstrated that persistence-prone viruses can suppress pDC-IFN-I production to debilitate the host immune system but IL-6 induction remains unaltered and becomes vital to control the chronic infection. |
