Instructor Houston Methodist Academic Inst. Houston, United States
Disclosure(s):
Abhishek Mishra, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
