ATP-dependent activation of NLRP3 inflammasome in primary murine macrophages infected by pseudorabies virus

Pseudorabies virus (PRV), an alphaherpesvirus, causes respiratory and reproductive diseases in pigs and severe nervous symptom in other susceptible hosts. Previous studies showed that PRV infection induced a systemic inflammatory response in mice, indicating that pro-inflammatory cytokines participated in viral neuropathy in mice. The pro-inflammatory cytokine IL-1 beta is a key mediator of the inflammatory response and plays an important role in host-response to pathogens. However, the secretion of IL-1 beta and its relationship with inflammasome activation during PRV infection remains poorly understood. In this study, we found that PRV infection caused significant secretion of several pro-inflammatory cytokines in macrophages and promoted IL-1 beta secretion in an ATP-dependent manner. Furthermore, the expression of IL-1 beta can be induced by only PRV infection and depended on NF-kappa B pathway activation, while the subsequent secretion of IL-1 beta was mediated by ATP-induced P2 x 7R activation, loss of intracellular K+, and the subsequent NLRP3 inflammasome activation. By using a mouse infection model, we also found that ATP exacerbated clinical signs and death of mice infected by PRV in a NLRP3-dependent manner. These results indicate that ATP facilitates activation of NLRP3 inflammasome and enhances the pathogenicity of PRV in mice during its acute infection.

Automated summary

PRV infection induces secretion of various pro-inflammatory cytokines and promotes IL-1 beta secretion, exacerbating inflammatory response in mice and causing severe damage to the host.