Integrative whole-transcriptome analysis of circRNAs, lncRNAs, miRNAs, and mRNAs reveals regulatory networks in mouse brain during Toxoplasma gondii infection.

Noncoding RNAs regulate distinct neuroinflammatory pathways during acute versus chronic toxoplasmosis.

This study employs RNA sequencing to comprehensively analyze differential expression of circular RNAs, long noncoding RNAs, microRNAs, and messenger RNAs in mouse brain tissue during acute and chronic phases of Toxoplasma gondii infection. Mice were orally infected with 20 cysts of the Pru strain. Results demonstrated significant transcriptome remodeling at both infection stages: acute infection showed alterations in 14 circRNAs, 427 lncRNAs, 105 miRNAs, and 1,490 mRNAs, while chronic infection involved 17 circRNAs, 581 lncRNAs, 131 miRNAs, and 2,646 mRNAs. Notably, 36 miRNAs and 782 mRNAs were dysregulated across both phases. Pathway analysis revealed acute-phase association with autophagy and PI3K-Akt signaling, whereas chronic infection involved neurotrophin and MAPK signaling pathways. The authors constructed competitive endogenous RNA networks elucidating complex regulatory interactions among noncoding RNAs that modulate host transcriptional responses. These findings illuminate the multifaceted regulatory mechanisms governing brain response to T. gondii infection, providing insights into toxoplasmosis pathogenesis.

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