Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-(IFN-),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate-adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Polygalacin D inhibits the growth of hepatocellular carcinoma cells through BNIP3L-mediated mitophagy and endogenous apoptosis pathways

Platycodon grandiflorum(Jacq.)A.DC.is a famous medicinal plant commonly used in East Asia.Triterpene saponins isolated from P.grandiflorum are the main biologically active compounds,among which polygalacin D(PGD)has been reported to be an anti-tumor agent.However,its anti-tumor mechanism against hepatocellular carcinoma is unknown.This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action.We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy.Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways.Subsequently,using specific inhibitors,we found that apoptosis and autophagy had mutually reinforcing effects.In addition,further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like(BNIP3L)levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors.Overall,our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways.Therefore,PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.