Porcine reproductive and respiratory syndrome virus infection activates IL-10 production through NF-κB and p38 MAPK pathways in porcine alveolar macrophages.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an emerging animal virus that has caused high economic losses for the swine industry worldwide. Previous in vitro and in vivo studies demonstrated that PRRSV infection induces significant production of interleukin 10 (IL-10), a pleiotropic cytokine with immuno-modulatory functions involved in host defense. However, the underlying regulatory mechanisms during PRRSV remain largely unknown. In the present study, we analyzed the expression kinetics of IL-10 in PRRSV-infected primary porcine alveolar macrophages (PAMs) and showed that PRRSV infection induced IL-10 mRNA and protein expression in a time- and dose-dependent manner. Inhibition of various molecules of the Toll-like receptor (TLR) or RIG-I-like receptor (RLR) signaling pathways demonstrated that the TLR adaptor myeloid differentiation primary response gene 88 (MyD88) has an important role in IL-10 induction during PRRSV infection. Furthermore, treatment with specific inhibitors or siRNA knockdown assays demonstrated that NF-κB and p38 MAPK (mitogen-activated protein kinase) are required for PRRSV-induced IL-10. Taken together, PRRSV infection significantly induced IL-10 expression and this induction depends on NF-κB activation and p38 MAPK in PAMs.