In vivo virus infection inhibits type I interferon production by plasmacytoid dendritic cells thereby facilitating opportunistic infections

Emerging in vitro and epidemiological studies indicate an association between virally-induced impaired type I interferon (IFN-I) production and enhanced susceptibility to opportunistic infections, which represent a major health problem. Here, we provide in vivo evidence that lymphocytic choriomeningitis virus (LCMV) infection of its natural host, the mouse, dramatically diminishes the unique capacity of plasmacytoid dendritic cells (pDCs) to secrete high levels of systemic IFN-I. While both acute and persistent LCMV infections suppress pDC IFN-I response, only the persistent virus induces a long-lasting diversion of this innate immune pathway. LCMV infection selectively affects the hallmark function of pDCs to produce prodigious amounts of IFN-I but does not alter their secretion of other cytokines, chemokines and maturation. This results in reduced IFN-I production and relates to impaired NK cell responses in LCMV-infected mice challenged with murine cytomegalovirus (MCMV) as an opportunistic pathogen. This innate immune-defect is associated with a compromised host ability to counteract early MCMV spread. Thus, an explanation for understanding the occurrence of opportunistic infections following in vivo viral insults is uncovered and has important implications for the alleviation and treatment of such medical complications.