Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells

Chinnaswamy Jagannath, Devin R. Lindsey, Subramanian Dhandayuthapani, Yi Xu, Robert L. Hunter, N. Tony Eissa

Research output: Contribution to journalArticle

340 Scopus citations

Abstract

The variable efficacy of Bacille Calmette Guerin (BCG) vaccination against tuberculosis has prompted efforts to improve the vaccine. In this study, we used autophagy to enhance vaccine efficacy against tuberculosis in a mouse model. We examined the effect of autophagy on the processing of the immunodominant mycobacterial antigen Ag85B by antigen presenting cells (APCs), macrophages and dendritic cells (DCs). We found that rapamycin-induced autophagy enhanced Ag85B presentation by APCs infected with wild-type Mycobacterium tuberculosis H37Rv, H37Rv-derived ΔfbpA attenuated candidate vaccine or BCG. Furthermore, rapamycin enhanced localization of mycobacteria with autophagosomes and lysosomes. Rapamycin-enhanced antigen presentation was attenuated when autophagy was suppressed by 3-methyladenine or by small interfering RNA against beclin-1. Notably, mice immunized with rapamycin-treated DCs infected with either ΔfbpA or BCG showed enhanced T helper type 1-mediated protection when challenged with virulent Mycobacterium tuberculosis. Finally, overexpression of Ag85B in BCG induced autophagy in APCs and enhanced immunogenicity in mice, suggesting that vaccine efficacy can be enhanced by augmenting autophagy-mediated antigen presentation.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalNature Medicine
Volume15
Issue number3
DOIs
StatePublished - Mar 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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