Porcine reproductive and respiratory syndrome virus modulates the main innate immune function of porcine plasmacytoid dendritic cells

摘要

Plasmacytoid dendritic cells (pDCs) represent less than 0.3% of the peripheral blood mononuclear cell (PBMC) population. Nevertheless, these cells can be distinguished from the other much more prevalent subsets of blood mononuclear cells such as macrophages, B cells and T cells by the lack of T and B cell receptors, as well as by the expression of CD4 in combination with the low-level expression of the macrophage marker CD172 (i.e., CD4+CD172low). Despite their scarcity, these cells are the most potent interferon-a (IFN-alpha) producing cells in either the peripheral blood or lymphoid tissues of an animal. Accordingly, these members of the innate immune system are primarily responsible for the initial protective innate immune response elicited during the acute stage of a virus infection and also play a pivotal role in regulating the adaptive immune response to viruses. Exposure of pDC to viruses or immunostimulatory CpG-containing synthetic oligodeoxynucleotides (CpG-ODN) usually induces a promptand copious secretion of interferon (IFN- alpha). However, based on the reported lack of or very limited presence of IFN-a in the lungs or plasma of pigs experiencing an acute infection with porcine reproductive and respiratory syndrome virus (PRRSV)4'5,it appears that this pathogen somehow circumvents this event. To clarify this issue we investigated the behavior of porcine pDCs exposed to PRRSV both in vitro and in vivo. Our results indicate that PRRSV not only fails to stimulate IFN-a production bythese cells but also inhibits their ability to produce this cytokine in response to otherwise potent stimulators of this molecule.