Artículo
A Brucella spp. protease inhibitor limits antigen lysosomal proteolysis, increases cross-presentation, and enhances CD8+ T Cell responses
Coria, Lorena M.; Ibañez, Andres Esteban
; Tkach, Mercedes
; Sabbione, Florencia
; Bruno, Laura; Carabajal, Marianela Veronica
; Berguer, Paula Mercedes
; Barrionuevo, Paula
; Schillaci, Roxana
; Trevani, Analía Silvina
; Giambartolomei, Guillermo Hernan
; Pasquevich, Karina Alejandra
; Cassataro, Juliana











Fecha de publicación:
15/05/2016
Editorial:
American Association of Immunologists
Revista:
Journal of Immunology
ISSN:
0022-1767
e-ISSN:
1550-6606
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Adjuvant
,
Cross-Presentation
,
Antitumor
,
Brucellosis
,
Immunotherapy Methods
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Articulos(IIBBA) [1078]
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(IMEX) [606]
Articulos de INST.DE MEDICINA EXPERIMENTAL
Articulos de INST.DE MEDICINA EXPERIMENTAL
Articulos(IBYME) [1500]
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Coria, Lorena M.; Ibañez, Andres Esteban; Tkach, Mercedes; Sabbione, Florencia; Bruno, Laura; et al.; A Brucella spp. protease inhibitor limits antigen lysosomal proteolysis, increases cross-presentation, and enhances CD8+ T Cell responses; American Association of Immunologists; Journal of Immunology; 196; 10; 15-5-2016; 4014-4029
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