title: Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells.
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 DeltafbpA 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 DeltafbpA 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center (UTHSC), 6431, Fannin, Houston, Texas 77030, USA. Chinnaswamy.Jagannath@uth.tmc.edu
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Jagannath
authors.forename: Devin R
authors.initials: DR
authors.lastname: Lindsey
authors.forename: Subramanian
authors.initials: S
authors.lastname: Dhandayuthapani
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hunter
authors.forename: N Tony
authors.initials: NT
authors.lastname: Eissa
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001343:Autophagy / Q000187:drug effects; D001500:BCG Vaccine / Q000276:immunology*; D003713:Dendritic Cells; D008247:Lysosomes / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D010588:Phagosomes / Q000187:drug effects / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D001500:BCG Vaccine; D010455:Peptides; D020123:Sirolimus