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

Chinnaswamy, J. et al. 2009. Nature Medicine. 15, 267-276

Student: Yu-Ping Chang (張鈺苹)                                 Time: 14:00~15:00, Sep. 23, 2009

Commentator: Dr. Huan-Yao Lei (黎煥耀 博士)                Place: Room 601

Abstract:

Autophagy is a physiological process, which mediates cytosolic component and organelle degradation by autophagosome. Additionally, autophagy is required for human innate and adaptive immunity by facilitating antigen presentation.¹ Recent studies had revealed that autophagy played a key role in inhibition of BCG and Mycobacterium tuberculosis (Mtb) survival in infected marcrophages.² In this study,³ the authors discovered that autophagy could enhance the presentation of Ag85B, a dominant immunogenic antigen secreted by Mtb,  by Mtb-infected antigen presenting cells (APCs) macrophages and dendritic cells. Mycobacteria itself and the secreted Ag85B were found to colocalized at autophagosomes and lysosomes after the induction of autophagy. Treatment of 3-methyladenine or autophagic inhibition by beclin-1 small interfering RNA reduced this phenomenon. Furthermore, result from C57BL/6 mice vaccinated with rapamycin-treated DCs infected with either Mtb or BCG demonstrated that rapamycin could enhance Ag85B specific T cell response in vivo. Moreover, rapamycin-DC-immunized mouse had increased amount of IFN-g⁺CD4⁺T cells and fewer mycobacteria in lungs compared to DC-immunized mouse. Overexpression of Ag85B in BCG induced a strong early protection against tuberculosis by enhancing BCG vaccine efficacy. Taken together, the efficacy of vaccines against tuberculosis can be enhanced through the modulation of autophagy in APCs.

References:

1.      Schmid, D. et al. 2007. Innate and adaptive immunity through autophagy. Immunity 27, 11-21.

2.      Gutierrez, M.G. et al. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753-766.

3.      Chinnaswamy, J. et al. 2009. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nature Medicine. 15, 267-276