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Antigen processing of Mycobacterium bovis BCG vaccine substrains differs in mouse dendritic cells 2259586

Year: 2026
Type: article
Abstract: Introduction The BCG vaccine given at birth varies in its protective efficacy against tuberculosis that kills millions of people. We hypothesized that this could be due to a heterogeneity among BCG sub strains. Therefore, we examined their ex vivo immunogenicity using dendritic cells. Methods The DC.2.4 cell line derived from C57BL/6 mice were infected with Pasteur, Copenhagen, Japan, Moreau, and Russian strains, followed by an assay for their ability to present Antigen85B-derived peptide to CD4 T cells triggering IL-2; RNAseq analysis for gene expression; and proteomics. Results 1) Antigen presentation by Copenhagen infected DCs to T cells was better than others. 2) RNAseq data analyzed using KEGG, GO and Reactome analyses indicated that Copenhagen infected DCs showed a better enrichment of genes Involved in antigen processing, autophagy and cytokine-chemokine modules compared to others. 3) Proteomics confirmed that the antigen processing machinery (Cathepsins, MHC and autophagy-mediating proteins) was differentially upregulated; Copenhagen showed the greatest enrichment followed by Russian, Moreau, Pasteur and Japan. Conclusion We propose that BCG sub strains differ in DC-dependent T cell activation, likely to affect protection against tuberculosis. Funding Source NIH NIAID R01-AI-I87440 Topic Categories Vaccines and Immunotherapy (VAC)
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W7171564786
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