Comparative analysis of Microtus fortis and murine hosts reveals a correlation between BRD4 and hepatic inflammation during Schistosoma japonicum infection.

BACKGROUND: Schistosomiasis, a parasitic disease affecting more than 240 million people worldwide, is characterized by chronic inflammation and tissue fibrosis primarily induced by parasite egg deposition. Bromodomain-containing protein 4 (BRD4), an epigenetic and transcriptional regulator, has emerged as a potential therapeutic target due to its dual role in modulating Schistosoma japonicum (S. japonicum) reproductive development and organ fibrosis. Despite these advances, the specific involvement of BRD4 in the host immune response during S. japonicum infection still remains completely unclear. METHODS: To explore the involvement of BRD4 in the immune response to S. japonicum, we performed a comparative time-series RNA-seq analysis of liver tissues from the non-permissive host Microtus fortis and the permissive host Mus musculus. BRD4-associated gene expression patterns were analyzed through correlation-based classification, followed by protein-protein interaction network construction and functional enrichment analyses. In addition, BRD4 was pharmacologically inhibited in vivo using JQ1, and hepatic inflammation and worm load were evaluated at 14 days post-infection. RESULTS: BRD4 displayed distinct transcriptional dynamics between M. fortis and M. musculus. Genes positively correlated with BRD4 expression were significantly enriched in inflammatory and immune-related pathways, including Th17 cell differentiation and hallmark inflammatory response. These patterns suggest a potential regulatory role for BRD4 in mediating hepatic inflammation during infection. In vivo inhibition of BRD4 with JQ1 reduced liver inflammation, further supporting its association with proinflammatory responses. CONCLUSIONS: Our findings reveal strong transcriptional correlations between BRD4 expression and immune activation, and further highlight BRD4 as a potential regulator of host inflammatory responses during S. japonicum infection. BRD4 may serve as a valuable molecular target for understanding host-pathogen interactions and developing adjunct therapies against schistosomiasis.