BCG overexpressing Ag85B reprograms host immune response through coordinated transcriptional networks

Previous studies have demonstrated that recombinant BCG strains overexpressing Ag85B (BCG85B) confer significant protection against tuberculosis in mouse models. This study hypothesized that enhanced protection by recombinant BCG (rBCG) results from modulation of host immune gene expression by the Ag85B antigen.

To test this, RNA-seq analysis was performed on splenocytes from mice immunized with the wild-type BCG (BCG-WT) and BCG85B strains. Differentially expressed genes (DEGs) in the splenocytes of BCG85B-immunized mice indicated upregulation of immune-related KEGG pathways, including Th1/Th2 and Th17 differentiation, NF-kappa B signaling, and cytokine-cytokine receptor interactions, as well as Gene Ontology (GO) processes such as immune response activation, α-β T cell activation, T-cell production and differentiation, IL-15 mediated signaling, and cytokine-mediated signaling pathways and down regulation of metabolic and digestive processes.