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BCG overexpressing Ag85B reprograms host immune response through coordinated transcriptional networks

ABSTRACT: Antigen 85B (Ag85B), an immunodominant protein secreted by Mycobacterium tuberculosis (Mtb), induces robust T-cell-mediated immunity in host cells. 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. Additionally, transcription factor (TF) and protein-protein interaction (PPI) analyses confirmed upregulation of genes involved in T cell receptor signaling and immune activation (Cd5, Zapp70, Icos, Ctla4, Gzmb, Cd3e, and Il7r) in splenocytes from BCG85B-immunized mice. Collectively, these findings indicate that Ag85B overexpression enhances adaptive immune activation and reprograms cellular metabolic pathways, thereby increasing vaccine efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE341826 | GEO | 2026/09/02

REPOSITORIES: GEO

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| PRJNA1504242 | ENA