Functional modulation of plazmacytoid dendritic cells during viral infections

Abstract

Plasmacytoid dendritic cells (pDCs), also known as interferon (IFN)-producing cells (IPCs), represent a unique cell population of innate immunity due to their ability to produce high amounts of type I IFNs in response to viral infections. The pDCs recognize viral nucleic acids via Toll-like receptor (TLR)7 and TLR9 localized in endosomal compartments. Type I IFNs, secreted by activated pDCs through the recognition of foreign nucleic acids, not only exhibit a direct antiviral activity but also activate NK cells, induce myeloid DC (mDC) maturation, promote T cell long-term survival and memory formation, polarization of Th1 cells, cytolytic activity of CD8+ T lymphocytes and IFN-γ production. Therefore, pDCs link innate and adaptive immunity to mount an effective antiviral immune response. The pDCs, which act as the main cells of innate immunity that produce type I IFNs, play an important role in controlling viral infections, including human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), lymphocytic choriomeningitis virus (LCMV), hepatitis C virus (HCV), hepatitis B virus (HBV), respiratory syncytial virus (RSV) and herpes simplex virus (HSV) infections. However, some of these viruses can infect and even replicate productively in pDCs, resulting in modulation and functional impairment of these cells. Thus, viruses evade host antiviral immune response to mediate a persistent infection.