Abstract
Severe liver inflammation, in which the interaction between circulating immune cells and hepatocytes plays a crucial role, is a major concern in acute viral hepatitis. Nevertheless, the mechanisms by which these circulating immune cells drive hepatocyte inflammatory responses remain inadequately understood. In this study, we demonstrate that the transcription of several notable proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, is markedly greater in cocultures of duck hepatitis A virus (DHAV)-infected hepatocytes than in hepatocytes infected with only DHAV. Simultaneously, the remodelling of the mature tRNAome in infected hepatocytes is orchestrated by coculturing peripheral blood mononuclear cells (PBMCs). Consistent with the effects of PBMC coculture, monocyte coculture also enhances the transcription of proinflammatory cytokines and the remodelling of the mature tRNAome in infected hepatocytes. These results indicate the importance of monocytes in orchestrating proinflammatory cytokine transcription and mature tRNAome remodelling in infected hepatocytes. Importantly, the coculture of monocytes with DHAV-infected hepatocytes not only regulates IL-1β transcription and mature tRNAome remodelling but also orchestrates protein translation within infected hepatocytes. Furthermore, neutralizing secreted IL-1β proteins influences the transcription of downstream cytokines associated with IL-1β signalling. Collectively, our findings reveal that monocytes play a crucial role in orchestrating the inflammatory response of hepatocytes through mechanisms involving the transcriptional activation of proinflammatory cytokines and the coordination of tRNAome remodelling-mediated translation.