# Orchestration of hepatocyte inflammatory responses by monocytes during acute viral hepatitis in ducks in vitro

## TL;DR

This study shows that monocytes help control liver cell inflammation during duck hepatitis by boosting cytokine production and altering RNA in infected cells.

## Contribution

The study reveals a novel role for monocytes in regulating hepatocyte inflammation through cytokine transcription and tRNAome remodelling during viral infection.

## Key findings

- Monocyte coculture increases proinflammatory cytokine transcription in DHAV-infected hepatocytes.
- Monocytes orchestrate tRNAome remodelling and protein translation in infected hepatocytes.
- Blocking IL-1β affects downstream cytokine transcription in infected hepatocytes.

## 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.

The online version contains supplementary material available at 10.1186/s13567-025-01630-9.