Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo.
Mast cells (MCs) are considered major players in IgE-mediated allergic responses, but have also recently been recognized as active participants in innate as well as specific immune responses. Recent work provided evidence that MCs are able to activate B and T lymphocytes through the release of vesicles called exosomes. Here we demonstrate that exosomes, which are located in the endocytic pathway, harbor exogenous Ags that associate with other molecules endowed with immunomodulatory functions, including 60- and 70-kDa heat shock proteins. Administration to naive mice of Ag-containing exosomes in the absence of conventional adjuvants elicits specific Ab responses across the MHC II haplotype barrier. We demonstrate that MC-exosomes induce immature dendritic cells (DCs) to up-regulate MHC class II, CD80, CD86, and CD40 molecules and to acquire potent Ag-presenting capacity to T cells. Uptake and processing of Ag-associated exosomes by endogenous DCs were also demonstrated. Finally, exosome-associated heat shock proteins are critical for the acquisition by DCs of the Ag-presenting function. This work demonstrates a heretofore unrecognized collaborative interaction between MCs and DCs leading to the elicitation of specific immune responses.
Skokos
Dimitris
D
Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
Botros
Hany Goubran
HG
Demeure
Christian
C
Morin
Joelle
J
Peronet
Roger
R
Birkenmeier
Gerd
G
Boudaly
Sarah
S
Mécheri
Salaheddine
S
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D014168:Transferrin / Q000276:immunology / Q000378:metabolism
D018834:Chaperonin 60; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D014168:Transferrin