# Transcriptional Profiling of the Rabbit Liver Infected With Eimeria stiedae Reveals Dynamic Host Cell Responses During the Induction and Resolution of Cholangitis

## TL;DR

This study uses RNA sequencing to track liver gene expression changes in rabbits infected with Eimeria stieda, revealing how the host responds during and after cholangitis.

## Contribution

The study provides new insights into host-pathogen interactions and liver self-healing mechanisms during parasitic cholangitis.

## Key findings

- Eimeria stiedae infection induces strong inflammatory and immune responses in rabbit livers.
- Liver self-healing is observed during late infection with reduced immune and metabolic dysfunction.
- RNA-seq reveals dynamic gene expression changes across infection stages, including metabolic and coagulation pathway disruptions.

## Abstract

Eimeria stiedae is one of the few eukaryotic pathogens that exclusively infect the liver and serves as a good model to study the host–pathogen interactions in this vital organ. In this study, we show that rabbits infected with E. stiedae develop severe but self-healing cholangitis. RNA-seq analysis of the liver gene expression landscapes over the long course of E. stiedae infection identified 912 differentially expressed genes (DEGs) in the prepatent period (794 up- and 118 downregulated genes), 2889 DEGs in the early oocyst shedding period (1870 up- and 1019 downregulated genes), 2859 DEGs in the peak oocyst shedding period (1923 up- and 936 downregulated genes), and 327 DEGs in the recovery period (164 up- and 163 downregulated genes). Combined with pathological observations, we identified dynamic changes in host–parasite interactions involving multiple pathways. They showed that E. stiedae infection induced full-blown inflammatory, Th1 and Th17 immune responses at all time points. This was associated with the strong innate immune responses during the prepatent period, including increased Toll-like and NOD-like receptor signaling. Despite mounting several damage control and repair responses, such as PI3K-Akt signaling, Ras signaling, and extracellular matrix-receptor interactions, the liver underwent severe metabolic dysfunction, oxidative damage, and coagulopathy after patency and at peak infection, possibly as a result of suppressed peroxisome activities and downregulated PPAR signaling. These responses largely disappeared during late infection, suggesting that the liver self-heals after severe cholangitis. These data provide new insights into host–pathogen interactions during Eimeria infection and improve our understanding of the pathogenesis of parasitic cholangitis.