Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens

The initiation of cytotoxic immune responses by dendritic cells (DCs) requires the presentation of antigenic peptides derived from phagocytosed microbes and infected or dead cells to CD8(+) T cells, a process called cross-presentation. Antigen cross-presentation by non-activated DCs, however, is not...

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Detalles Bibliográficos
Autores: Alloatti, Andrés, Kotsias, Fiorella, Pauwels, Anne Marie, Carpier, Jean Marie, Jouve, Mabel, Timmerman, Evy, Pace, Luigia, Vargas, Pablo, Maurin, Mathieu, Gehrmann, Ulf, Joannas, Leonel, Vivar, Omar I., Lennon Duménil, Ana Maria, Savina, Ariel, Gevaert, Kris, Beyaert, Rudi, Hoffmann, Eik, Amigorena, Sebastian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/44344
Acceso en línea:http://hdl.handle.net/11336/44344
Access Level:acceso abierto
Palabra clave:Gtpase Rab34
Toll-Like Receptor 4
Antigen Presentation
Cross-Presentation
Dendritic Cell
Phagocytosis
Phagosome Maturation
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:The initiation of cytotoxic immune responses by dendritic cells (DCs) requires the presentation of antigenic peptides derived from phagocytosed microbes and infected or dead cells to CD8(+) T cells, a process called cross-presentation. Antigen cross-presentation by non-activated DCs, however, is not sufficient for the effective induction of immune responses. Additionally, DCs need to be activated through innate receptors, like Toll-like receptors (TLRs). During DC maturation, cross-presentation efficiency is first upregulated and then turned off. Here we show that during this transient phase of enhanced cross-presentation, phago-lysosome fusion was blocked by the topological re-organization of lysosomes into perinuclear clusters. LPS-induced lysosomal clustering, inhibition of phago-lysosome fusion and enhanced cross-presentation, all required expression of the GTPase Rab34. We conclude that TLR4 engagement induces a Rab34-dependent re-organization of lysosomal distribution that delays antigen degradation to transiently enhance cross-presentation, thereby optimizing the priming of CD8(+) T cell responses against pathogens.

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