Artículo
TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display
Molinari, Maria Paula
; Crespo, Maria Ines
; Molina, Guido Nicolás
; Dho, Nicolás Daniel
; Marinho, Fábio A. V.; Maletto, Belkys Angélica
; Leclerc, Claude; Oliveira, Sergio C.; Taboga, Oscar Alberto
; Cebrián, José Ignacio
; Morón, Sergio Gabriel
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Fecha de publicación:
24/11/2022
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
Immunology
ISSN:
0019-2805
e-ISSN:
1365-2567
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Although the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A novel strategy based on capsid display carrying foreign antigens in the AcMNPV particle further improved the immune response by eliciting CD8+ T cell activation. In this study, we analyze the intracellular mechanisms and signalling pathways involved in CD8+ T cell activation by capsid display. Our results show that baculovirus can attach to the cell surface, enter dendritic cells (DCs), transit within endocytic vesicles and escape to the cytosol for further degradation by the proteasome. We found that the availability of viral proteins, endosomal acidification, and proteasome activity are needed for efficient Major Histocompatibility Complex class-I presentation by baculovirus carrying Ovalbumin in the viral capsid. Importantly, we demonstrated with this strategy that the induction of cytotoxic T cells and IL-12 production by DCs are TLR9-dependent and STING-independent. Finally, our study shows differential intracellular processing for capsid and surface baculovirus proteins in DCs and highlights the role of different danger receptors during cytotoxic T cell priming through the capsid display delivery system, which could lead to improved baculovirus-based vaccines development.
Palabras clave:
ACMNPV
,
ANTIGEN CROSS-PRESENTATION
,
BACULOVIRUS
,
CAPSID DISPLAY
,
CTL
,
TLR9
Archivos asociados
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Identificadores
Colecciones
Articulos (IABIMO)
Articulos de INSTITUTO DE AGROBIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Articulos de INSTITUTO DE AGROBIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Molinari, Maria Paula; Crespo, Maria Ines; Molina, Guido Nicolás; Dho, Nicolás Daniel; Marinho, Fábio A. V.; et al.; TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display; Wiley Blackwell Publishing, Inc; Immunology; 169; 1; 24-11-2022; 27-41
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