期刊
NATURE MEDICINE
卷 15, 期 3, 页码 267-276出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1928
关键词
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资金
- US National Institutes of Health National Institute of Allergy and Infectious Diseases [AI49534]
- National Heart, Lung, and Blood Institute [HL080205]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL080205] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P30AI036211, R01AI049534] Funding Source: NIH RePORTER
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 Delta fbpA 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 DfbpA 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.
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