NDV-induced autophagy enhances inflammation through NLRP3/Caspase-1 inflammasomes and the p38/MAPK pathway

Newcastle disease (ND), caused by the Newcastle disease virus (NDV), is a highly virulent infectious disease of poultry. Virulent NDV can cause severe Autophagy and inflammation in host cells. While studies have shown a mutual regulatory relationship between Autophagy and inflammation, this relationship in NDV Infection remains unclear. This study confirmed that NDV Infection could trigger Autophagy in DF-1 cells to promote cytopathic and viral replication. NDV-induced Autophagy was positively correlated with the mRNA levels of inflammatory cytokines such as IL-1β, IL-8, IL-18, CCL-5, and TNF-α, suggesting that NDV-induced Autophagy promotes the expression of inflammatory cytokines. Further investigation demonstrated that NLRP3 protein expression, Caspase-1 activity, and p38 phosphorylation level positively correlated with Autophagy, suggesting that NDV-induced Autophagy could promote the expression of inflammatory cytokines through NLRP3/Caspase-1 inflammasomes and p38/MAPK pathway. In addition, NDV Infection also triggered mitochondrial damage and Mitophagy in DF-1 cells, but did not result in a large leakage of Reactive Oxygen Species (ROS) and mitochondrial DNA (mtDNA), indicating that mitochondrial damage and Mitophagy do not contribute to the inflammation response during NDV Infection.