School of Medicine Publications
Document Type
Article
Publication Date
8-12-2026
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 BCG85B 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, Zap70, 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.
Recommended Citation
Chauhan, V., Kumar, R., Veerapandian, R., Ramos, E. I., Jagannath, C., Gadad, S. S., & Dhandayuthapani, S. (2026). BCG overexpressing Ag85B reprograms host immune response through coordinated transcriptional networks. Frontiers in Immunology, 17, 1876830. https://doi.org/10.3389/fimmu.2026.1876830
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Frontiers in Immunology
DOI
10.3389/fimmu.2026.1876830
Academic Level
faculty
Mentor/PI Department
Immunology and Microbiology
Comments
© 2026 Chauhan, Kumar, Veerapandian, Ramos, Jagannath, Gadad and Dhandayuthapani.
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