Transcriptomic Profiling of mRNAs , circRNAs , and lncRNAs in Mouse Liver at the Early Stage of Echinococcus multilocularis Infection

ABSTRACT Alveolar echinococcosis (AE) is a significant zoonotic disease caused by the larval form of Echinococcus multilocularis ( E. multilocularis ), posing substantial health risks. However, the roles of circular RNAs (circRNAs), long non‐coding RNAs (lncRNAs), and messenger RNAs (mRNAs) in the early stages of E. multilocularis infection, particularly regarding liver involvement, remain unclear. This study aimed to investigate the molecular mechanisms of AE infection in mice during the early stage of secondary infection. The expression profiles of mRNAs, circRNAs and lncRNAs in mouse livers were analyzed at four time points: 2, 4, 8, and 15 days post‐infection (dpi). The results identified a substantial number of differentially expressed molecules, including 5004 circRNAs and 8744 lncRNAs. These differentially expressed ncRNAs were mainly involved in immune‐related categories, such as antigen processing and presentation and T cell activation. Interactions among circRNAs, lncRNAs, and immune‐associated mRNAs formed competing endogenous RNAs (ceRNAs) regulatory networks. Notably, mmu_circ_0008646 showed strong associations with microRNAs such as mmu‐miR‐466b‐3p and mmu‐miR‐574‐5p, while several lncRNAs also interacted with mmu‐miR‐574‐5p. miR‐574‐5p regulates inflammatory responses and macrophage polarization primarily through the NF‐κB pathway. Additionally, different components of E. multilocularis larva distinctively affect macrophage polarization, with the cystic fluid promoting macrophage M2 polarization and protoscoleces stimulating macrophage M1 polarization. This study highlights alterations in circRNA, lncRNA, and mRNA expression patterns in the livers of mice infected with E. multilocularis , enhancing our understanding of the AE transcriptomic profile.