Artículo
Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia
; Swallow, Maxine; Bartel, Judith; Lycke, Nils Yngve; Barkan, Daniel; Martina, Mariana Andrea
; Lujan, Hugo Daniel
; Kalay, Hakan; van Kooyk, Yvette; Sparwasser, Tim D.; Berod, Luciana
Fecha de publicación:
03/2018
Editorial:
Frontiers Media S.A.
Revista:
Frontiers in Immunology
ISSN:
1664-3224
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections.
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Articulos(CIDIE)
Articulos de CENTRO DE INV. Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Articulos de CENTRO DE INV. Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; et al.; Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses; Frontiers Media S.A.; Frontiers in Immunology; 9; MAR; 3-2018; 1-14
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