Investigating the innate type I interferon response in porcine antigen-presenting cells: focus on the effects of porcine reproductive and respiratory syndrome virus (PRRSV)

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important disease of swine worldwide and mechanisms governing activation of the innate immune response remain to be elucidated. Antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), are key players in both the innate and adaptive immune response. Lung-DCs play a role in antiviral immunity by providing early innate protection against viral replication and by presenting antigen to T-cells for initiation of the adaptive immune response. Alveolar macrophages reside in the airway and also play a role in innate immunity by inhibiting viral replication and producing proinflammatory cytokines for activation of the adaptive response. Type I interferons, such as interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta), are produced by cells recognizing conserved viral epitopes, such as double-stranded RNA (dsRNA), an intermediate of viral replication. Once produced, IFN-alpha and IFN-beta can induce the production of antiviral mediators, such as Mx and PKR, which are involved in inhibiting viral replication. Type I interferons also activate APCs for subsequent activation of naive T-cells for generating antigen-specific immune responses. Previous studies indicate that the adaptive response to PRRSV is suboptimal, as neutralizing antibody and antigen-specific, IFN-gamma producing T-cells are not measured until nearly four weeks after PRRSV infection. Therefore, we examined the activation of the innate type I interferon response to PRRSV in APCs, as this event is central to downstream control of viral replication and activation of the adaptive response. Taken together, results indicate that APCs do not produce enhanced levels of IFN-alpha or IFN-beta after exposure to PRRSV. In addition, expression of molecules involved in antigen presentation, such as major histocompatability complex (MHC) class I and co-stimulatory molecules CD80 and CD86, do not increase after PRRSV infection. However, alveolar macrophages do produce IFN-alpha and IFN-beta after exposure to dsRNA as well as increasing expression of both MHC class I and CD80/86. Overall, the lack of type I interferon response by lung-DCs and alveolar macrophages after PRRSV is significant and future studies designed to identify the mechanism in which PRRSV evades activation of the type I interferon response are critical for fully understanding PRRSV pathogenesis