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

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
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Alloatti, Andrés. Inserm; Francia. Institute Curie; Francia
Fil: Kotsias, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Institute Curie; Francia. Inserm; Francia. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento Virologia; Argentina
Fil: Pauwels, Anne Marie. University of Ghent; Bélgica
Fil: Carpier, Jean Marie. Institute Curie; Francia. Inserm; Francia
Fil: Jouve, Mabel. Institute Curie; Francia
Fil: Timmerman, Evy. University of Ghent; Bélgica
Fil: Pace, Luigia. Institute Curie; Francia. Inserm; Francia
Fil: Vargas, Pablo. Institute Curie; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Maurin, Mathieu. Institute Curie; Francia. Inserm; Francia
Fil: Gehrmann, Ulf. Institute Curie; Francia. Inserm; Francia
Fil: Joannas, Leonel. Institute Curie; Francia. Inserm; Francia
Fil: Vivar, Omar I.. Institute Curie; Francia. Inserm; Francia
Fil: Lennon Duménil, Ana Maria. Institute Curie; Francia. Inserm; Francia
Fil: Savina, Ariel. Institute Curie; Francia. Inserm; Francia. Roche SAS; Francia
Fil: Gevaert, Kris. University of Ghent; Bélgica
Fil: Beyaert, Rudi. University of Ghent; Bélgica
Fil: Hoffmann, Eik. Inserm; Francia. Institute Curie; Francia. University of Ghent; Bélgica
Fil: Amigorena, Sebastian. Inserm; Francia. Institute Curie; Francia
Materia
Gtpase Rab34
Toll-Like Receptor 4
Antigen Presentation
Cross-Presentation
Dendritic Cell
Phagocytosis
Phagosome Maturation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/44344
Acceder
id CONICETDig_11e565d5effa51e3075b5663e0e61bd7
oai_identifier_str oai:ri.conicet.gov.ar:11336/44344
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of AntigensAlloatti, AndrésKotsias, FiorellaPauwels, Anne MarieCarpier, Jean MarieJouve, MabelTimmerman, EvyPace, LuigiaVargas, PabloMaurin, MathieuGehrmann, UlfJoannas, LeonelVivar, Omar I.Lennon Duménil, Ana MariaSavina, ArielGevaert, KrisBeyaert, RudiHoffmann, EikAmigorena, SebastianGtpase Rab34Toll-Like Receptor 4Antigen PresentationCross-PresentationDendritic CellPhagocytosisPhagosome Maturationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The 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.Fil: Alloatti, Andrés. Inserm; Francia. Institute Curie; FranciaFil: Kotsias, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Institute Curie; Francia. Inserm; Francia. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento Virologia; ArgentinaFil: Pauwels, Anne Marie. University of Ghent; BélgicaFil: Carpier, Jean Marie. Institute Curie; Francia. Inserm; FranciaFil: Jouve, Mabel. Institute Curie; FranciaFil: Timmerman, Evy. University of Ghent; BélgicaFil: Pace, Luigia. Institute Curie; Francia. Inserm; FranciaFil: Vargas, Pablo. Institute Curie; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Maurin, Mathieu. Institute Curie; Francia. Inserm; FranciaFil: Gehrmann, Ulf. Institute Curie; Francia. Inserm; FranciaFil: Joannas, Leonel. Institute Curie; Francia. Inserm; FranciaFil: Vivar, Omar I.. Institute Curie; Francia. Inserm; FranciaFil: Lennon Duménil, Ana Maria. Institute Curie; Francia. Inserm; FranciaFil: Savina, Ariel. Institute Curie; Francia. Inserm; Francia. Roche SAS; FranciaFil: Gevaert, Kris. University of Ghent; BélgicaFil: Beyaert, Rudi. University of Ghent; BélgicaFil: Hoffmann, Eik. Inserm; Francia. Institute Curie; Francia. University of Ghent; BélgicaFil: Amigorena, Sebastian. Inserm; Francia. Institute Curie; FranciaCell Press2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/44344Alloatti, Andrés; Kotsias, Fiorella; Pauwels, Anne Marie; Carpier, Jean Marie; Jouve, Mabel; et al.; Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens; Cell Press; Immunity; 43; 6; 12-2015; 1087-11001074-76131097-4180CONICET DigitalCONICETenginfo:eu-repo/semantics/reference/doi/https://doi.org/10.1016/j.immuni.2015.11.013info:eu-repo/semantics/reference/url/https://www.sciencedirect.com/science/article/pii/S1074761315004914info:eu-repo/semantics/altIdentifier/url/https://www.cell.com/immunity/fulltext/S1074-7613(15)00458-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761315004586%3Fshowall%3Dtrueinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.immuni.2015.11.006info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:16:06Zoai:ri.conicet.gov.ar:11336/44344instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:16:06.409CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
title Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
spellingShingle Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
Alloatti, Andrés
Gtpase Rab34
Toll-Like Receptor 4
Antigen Presentation
Cross-Presentation
Dendritic Cell
Phagocytosis
Phagosome Maturation
title_short Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
title_full Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
title_fullStr Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
title_full_unstemmed Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
title_sort Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens
dc.creator.none.fl_str_mv 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
author Alloatti, Andrés
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Gtpase Rab34
Toll-Like Receptor 4
Antigen Presentation
Cross-Presentation
Dendritic Cell
Phagocytosis
Phagosome Maturation
topic Gtpase Rab34
Toll-Like Receptor 4
Antigen Presentation
Cross-Presentation
Dendritic Cell
Phagocytosis
Phagosome Maturation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Alloatti, Andrés. Inserm; Francia. Institute Curie; Francia
Fil: Kotsias, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Institute Curie; Francia. Inserm; Francia. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento Virologia; Argentina
Fil: Pauwels, Anne Marie. University of Ghent; Bélgica
Fil: Carpier, Jean Marie. Institute Curie; Francia. Inserm; Francia
Fil: Jouve, Mabel. Institute Curie; Francia
Fil: Timmerman, Evy. University of Ghent; Bélgica
Fil: Pace, Luigia. Institute Curie; Francia. Inserm; Francia
Fil: Vargas, Pablo. Institute Curie; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Maurin, Mathieu. Institute Curie; Francia. Inserm; Francia
Fil: Gehrmann, Ulf. Institute Curie; Francia. Inserm; Francia
Fil: Joannas, Leonel. Institute Curie; Francia. Inserm; Francia
Fil: Vivar, Omar I.. Institute Curie; Francia. Inserm; Francia
Fil: Lennon Duménil, Ana Maria. Institute Curie; Francia. Inserm; Francia
Fil: Savina, Ariel. Institute Curie; Francia. Inserm; Francia. Roche SAS; Francia
Fil: Gevaert, Kris. University of Ghent; Bélgica
Fil: Beyaert, Rudi. University of Ghent; Bélgica
Fil: Hoffmann, Eik. Inserm; Francia. Institute Curie; Francia. University of Ghent; Bélgica
Fil: Amigorena, Sebastian. Inserm; Francia. Institute Curie; Francia
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/44344
Alloatti, Andrés; Kotsias, Fiorella; Pauwels, Anne Marie; Carpier, Jean Marie; Jouve, Mabel; et al.; Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens; Cell Press; Immunity; 43; 6; 12-2015; 1087-1100
1074-7613
1097-4180
CONICET Digital
CONICET
url http://hdl.handle.net/11336/44344
identifier_str_mv Alloatti, Andrés; Kotsias, Fiorella; Pauwels, Anne Marie; Carpier, Jean Marie; Jouve, Mabel; et al.; Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens; Cell Press; Immunity; 43; 6; 12-2015; 1087-1100
1074-7613
1097-4180
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/doi/https://doi.org/10.1016/j.immuni.2015.11.013
info:eu-repo/semantics/reference/url/https://www.sciencedirect.com/science/article/pii/S1074761315004914
info:eu-repo/semantics/altIdentifier/url/https://www.cell.com/immunity/fulltext/S1074-7613(15)00458-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761315004586%3Fshowall%3Dtrue
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.immuni.2015.11.006
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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