CIDIE   24052
CENTRO DE INVESTIGACION Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Unidad Ejecutora - UE
artículos
Título:
Targeting Mycobacterium tuberculosis antigens to dendritic cells via the DC-specific-ICAM3-grabbing-nonintegrin receptor induces strong T-helper 1 immune responses
Autor/es:
GENTILINI, MARIA VIRGINIA; LYCKE, NILS YNGVE; LUJAN, HUGO D.; SPARWASSER, TIM D.; STÜVE, PHILIPP; BARTEL, JUDITH; VELASQUEZ, LIS NOELIA; MARTINA, MARIANA; SWALLOW, MAXINE; VAN KOOYK, YVETTE; BARKAN, DANIEL; KALAY, HAKAN; BEROD, LUCIANA; GENTILINI, MARIA VIRGINIA; LYCKE, NILS YNGVE; LUJAN, HUGO D.; STÜVE, PHILIPP; SPARWASSER, TIM D.; BARTEL, JUDITH; MARTINA, MARIANA; VAN KOOYK, YVETTE; VELASQUEZ, LIS NOELIA; SWALLOW, MAXINE; BARKAN, DANIEL; KALAY, HAKAN; BEROD, LUCIANA
Revista:
Frontiers in Immunology
Editorial:
Frontiers Media S.A.
Referencias:
Año: 2018 vol. 9
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.