Distinct temporal patterns of liver immune responses to pathogenic and non-pathogenic Entamoeba histolytica clones

Entamoeba histolytica is a protozoan parasite that can cause severe liver disease known as amoebic liver abscess. However, only a subset of infected individuals develops invasive disease, indicating that host-parasite interactions are critical determinants of disease outcome. In this study, we investigated the clone-specific modulation of hepatic immune responses using the non-pathogenic A1np and the pathogenic B2p E. histolytica clones. Time-resolved transcriptome analyses (6, 12, 24 hours post-infection, (hpi)) in a murine model revealed distinct immune trajectories. Both clones activated innate immune pathways early after infection, but their responses differed markedly in magnitude and composition. A1np infection induced a rapid and controlled inflammatory response associated with antimicrobial activity and resolution-promoting signalling. In contrast, B2p infection triggered a stronger and more complex immune response characterised by pronounced cytokine and chemokine expression, activation of stress and redox pathways, and tissue remodelling processes. By 24 hpi, the B2p induced response exhibited features of excessive immune activation, accompanied by the upregulation of counter-regulation genes such as Ackr2 and Il1rn. These findings indicate that liver pathology is not solely determined by parasite presence, but rather by the nature and regulation of the host immune response. Overall, the observed differences between A1np and B2p infections suggest that parasite-specific properties shape hepatic immune activation and may influence disease progression.