Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells
Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells
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DOI：
10.1038/nm.1928
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发表时间：
2009-03-01
期刊：
影响因子：
82.9
通讯作者：
Eissa, N. Tony
中科院分区：
文献类型：
--
作者：
Jagannath, Chinnaswamy;Lindsey, Devin R.;Eissa, N. Tony
卡介苗（BCG）疫苗接种对结核病的可变效力促使人们努力改进疫苗。在这项研究中，我们在小鼠模型中使用自噬来增强疫苗对结核病的效力。我们研究了自噬对抗原呈递细胞（APC）、巨噬细胞和树突状细胞（DC）处理免疫显性分枝杆菌抗原Ag 85 B的影响。我们发现雷帕霉素诱导的自噬增强了野生型结核分枝杆菌H37 Rv、H37 Rv衍生的Delta fbpA减毒候选疫苗或BCG感染的APC对Ag 85 B的呈递。此外，雷帕霉素增强了自噬体和溶酶体对分枝杆菌的定位。雷帕霉素增强的抗原呈递减弱时，自噬被抑制3-甲基腺嘌呤或小干扰RNA对beclin-1。值得注意的是，用雷帕霉素处理的DCs免疫的小鼠在用毒性结核分枝杆菌攻击时表现出增强的1型辅助性T细胞介导的保护作用。最后，BCG中Ag 85 B的过表达诱导了APC中的自噬，并增强了小鼠的免疫原性，这表明可以通过增强自噬介导的抗原呈递来增强疫苗功效。
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.