Autophagy Enhances the Efficacy of BCG Vaccine by Increasing Peptide Presentation in Mouse Dendritic Cells

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2009 Mar 3

PMID 19252503

Citations 263

Authors

Chinnaswamy Jagannath

Devin R Lindsey

Subramanian Dhandayuthapani

Yi Xu

Robert L Hunter Jr

N Tony Eissa

Affiliations

Soon will be listed here.

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.

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References

Miller B, Fratti R, Poschet J, Timmins G, Master S, Burgos M . Mycobacteria inhibit nitric oxide synthase recruitment to phagosomes during macrophage infection. Infect Immun. 2004; 72(5):2872-8. PMC: 387846. DOI: 10.1128/IAI.72.5.2872-2878.2004. View

Harth G, Lee B, Wang J, Clemens D, Horwitz M . Novel insights into the genetics, biochemistry, and immunocytochemistry of the 30-kilodalton major extracellular protein of Mycobacterium tuberculosis. Infect Immun. 1996; 64(8):3038-47. PMC: 174185. DOI: 10.1128/iai.64.8.3038-3047.1996. View

Vergne I, Chua J, Deretic V . Mycobacterium tuberculosis phagosome maturation arrest: selective targeting of PI3P-dependent membrane trafficking. Traffic. 2003; 4(9):600-6. DOI: 10.1034/j.1600-0854.2003.00120.x. View

Nathan C, Shiloh M . Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci U S A. 2000; 97(16):8841-8. PMC: 34021. DOI: 10.1073/pnas.97.16.8841. View

Noss E, Harding C, Boom W . Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages. Cell Immunol. 2000; 201(1):63-74. DOI: 10.1006/cimm.2000.1633. View

Gupta U, Katoch V, McMurray D . Current status of TB vaccines. Vaccine. 2007; 25(19):3742-51. DOI: 10.1016/j.vaccine.2007.01.112. View

Levine T, Chain B . The cell biology of antigen processing. Crit Rev Biochem Mol Biol. 1991; 26(5-6):439-73. DOI: 10.3109/10409239109086790. View

Ramachandra L, Noss E, Boom W, Harding C . Processing of Mycobacterium tuberculosis antigen 85B involves intraphagosomal formation of peptide-major histocompatibility complex II complexes and is inhibited by live bacilli that decrease phagosome maturation. J Exp Med. 2001; 194(10):1421-32. PMC: 2193679. DOI: 10.1084/jem.194.10.1421. View

Horwitz M, Harth G, Dillon B, Maslesa-Galic S . A novel live recombinant mycobacterial vaccine against bovine tuberculosis more potent than BCG. Vaccine. 2005; 24(10):1593-600. DOI: 10.1016/j.vaccine.2005.10.002. View

10.

Pancholi P, Mirza A, Bhardwaj N, Steinman R . Sequestration from immune CD4+ T cells of mycobacteria growing in human macrophages. Science. 1993; 260(5110):984-6. DOI: 10.1126/science.8098550. View

11.

Amano A, Nakagawa I, Yoshimori T . Autophagy in innate immunity against intracellular bacteria. J Biochem. 2006; 140(2):161-6. DOI: 10.1093/jb/mvj162. View

12.

Mazzaccaro R, Stenger S, Rock K, Porcelli S, Brenner M, Modlin R . Cytotoxic T lymphocytes in resistance to tuberculosis. Adv Exp Med Biol. 1999; 452:85-101. DOI: 10.1007/978-1-4615-5355-7_11. View

13.

Moulton R, Mashruwala M, Smith A, Lindsey D, Wetsel R, Haviland D . Complement C5a anaphylatoxin is an innate determinant of dendritic cell-induced Th1 immunity to Mycobacterium bovis BCG infection in mice. J Leukoc Biol. 2007; 82(4):956-67. DOI: 10.1189/jlb.0206119. View

14.

Dean R . Lysosomes and protein degradation. Acta Biol Med Ger. 1977; 36(11-12):1815-20. View

15.

Skeiky Y, Sadoff J . Advances in tuberculosis vaccine strategies. Nat Rev Microbiol. 2006; 4(6):469-76. DOI: 10.1038/nrmicro1419. View

16.

Armitige L, Jagannath C, Wanger A, Norris S . Disruption of the genes encoding antigen 85A and antigen 85B of Mycobacterium tuberculosis H37Rv: effect on growth in culture and in macrophages. Infect Immun. 2000; 68(2):767-78. PMC: 97204. DOI: 10.1128/IAI.68.2.767-778.2000. View

17.

Copenhaver R, Sepulveda E, Armitige L, Actor J, Wanger A, Norris S . A mutant of Mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Infect Immun. 2004; 72(12):7084-95. PMC: 529100. DOI: 10.1128/IAI.72.12.7084-7095.2004. View

18.

Griffin J, Orme I . Evolution of CD4 T-cell subsets following infection of naive and memory immune mice with Mycobacterium tuberculosis. Infect Immun. 1994; 62(5):1683-90. PMC: 186383. DOI: 10.1128/iai.62.5.1683-1690.1994. View

19.

Rohde K, Yates R, Purdy G, Russell D . Mycobacterium tuberculosis and the environment within the phagosome. Immunol Rev. 2007; 219:37-54. DOI: 10.1111/j.1600-065X.2007.00547.x. View

20.

Gutierrez M, Master S, Singh S, Taylor G, Colombo M, Deretic V . Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004; 119(6):753-66. DOI: 10.1016/j.cell.2004.11.038. View