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A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 May 15; Vol. 196 (10), pp. 4014-29. Date of Electronic Publication: 2016 Apr 15. - Publication Year :
- 2016
-
Abstract
- In this study, we demonstrate that the unlipidated (U) outer membrane protein (Omp) 19 from Brucella spp. is a competitive inhibitor of human cathepsin L. U-Omp19 inhibits lysosome cathepsins and APC-derived microsome activity in vitro and partially inhibits lysosomal cathepsin L activity within live APCs. Codelivery of U-Omp19 with the Ag can reduce intracellular Ag digestion and increases Ag half-life in dendritic cells (DCs). U-Omp19 retains the Ag in Lamp-2(+) compartments after its internalization and promotes a sustained expression of MHC class I/peptide complexes in the cell surface of DCs. Consequently, U-Omp19 enhances Ag cross-presentation by DCs to CD8(+) T cells. U-Omp19 s.c. delivery induces the recruitment of CD11c(+)CD8α(+) DCs and monocytes to lymph nodes whereas it partially limits in vivo Ag proteolysis inside DCs. Accordingly, this protein is able to induce CD8(+) T cell responses in vivo against codelivered Ag. Antitumor responses were elicited after U-Omp19 coadministration, increasing survival of mice in a murine melanoma challenge model. Collectively, these results indicate that a cysteine protease inhibitor from bacterial origin could be a suitable component of vaccine formulations against tumors.<br /> (Copyright © 2016 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Antigens, Neoplasm immunology
Cross-Priming
Female
Lymphocyte Activation
Lysosomal-Associated Membrane Protein 2 metabolism
Melanoma immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Antigens, Bacterial metabolism
Bacterial Outer Membrane Proteins metabolism
Brucella immunology
Brucellosis immunology
CD8-Positive T-Lymphocytes physiology
Cancer Vaccines immunology
Cathepsins metabolism
Dendritic Cells immunology
Immunotherapy methods
Lipoproteins metabolism
Lysosomes metabolism
Melanoma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 196
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 27084100
- Full Text :
- https://doi.org/10.4049/jimmunol.1501188