Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response
Autor: | Carmelo Biondo, Rossella Sartorius, Maria Giovanna De Leo, Fausta Cuccaro, Vincenzo Manuel Marzullo, Maria Trovato, Piergiuseppe De Berardinis, Luciana D'Apice, Maria Antonietta De Matteis, Alfredo Ciccodicola, Sabato D'Auria, Valerio Costa |
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Přispěvatelé: | Sartorius, Rossella, D'Apice, Luciana, Trovato, Maria, Cuccaro, Fausta, Costa, Valerio, De Leo, Maria Giovanna, Marzullo, Vincenzo Manuel, Biondo, Carmelo, D'Auria, Sabato, DE MATTEIS, Maria Antonietta, Ciccodicola, Alfredo, De Berardinis, Piergiuseppe |
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Receptors
Cell Surface CD8-Positive T-Lymphocytes Dendritic Cell Microbiology Minor Histocompatibility Antigens TLR9 Immune system Inovirus Antigen Adjuvants Immunologic Antigens CD Inoviru parasitic diseases Animals DEC-205 antigen delivery dendritic cells filamentous bacteriophage Lectins C-Type Single-Chain Antibodie DEC‐205 Antigens Cell Surface Display Technique Drug Carrier Late endosome Research Articles Cells Cultured Drug Carriers Innate immune system biology Animal Immunogenicity Gene Expression Profiling CD8-Positive T-Lymphocyte biology.organism_classification Filamentous bacteriophage fd Immunity Innate Minor Histocompatibility Antigen Mice Inbred C57BL Filamentous bacteriophage Toll-Like Receptor 9 Molecular Medicine Cell Surface Display Techniques Single-Chain Antibodies antigen delivery DEC‐205 dendritic cells filamentous bacteriophage TLR9 |
Zdroj: | EMBO molecular medicine (Online) (2015). doi:10.15252/emmm.201404525 info:cnr-pdr/source/autori:Sartorius R, D'Apice L, Trovato M, Cuccaro F, Costa V, De Leo MG, Marzullo VM, Biondo C, D'Auria S, De Matteis MA, Ciccodicola A, De Berardinis P./titolo:Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response./doi:10.15252%2Femmm.201404525/rivista:EMBO molecular medicine (Online)/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume EMBO Molecular Medicine EMBO molecular medicine 7 (2015): 973–988. doi:10.15252/emmm.201404525 info:cnr-pdr/source/autori:Sartorius R, D'Apice L, Trovato M, Cuccaro F, Costa V, De Leo MG, Marzullo VM, Biondo C, D'Auria S, De Matteis MA, Ciccodicola A, De Berardinis P./titolo:Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response./doi:10.15252%2Femmm.201404525/rivista:EMBO molecular medicine (Print)/anno:2015/pagina_da:973/pagina_a:988/intervallo_pagine:973–988/volume:7 |
Popis: | Filamentous bacteriophage fd particles delivering antigenic determinants via DEC‐205 (fdsc‐αDEC) represent a powerful delivery system that induces CD8 + T‐cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells. In order to investigate the mechanisms of this activity, RNA‐Sequencing of fd‐pulsed dendritic cells was performed. A significant differential expression of genes involved in innate immunity, co‐stimulation and cytokine production was observed. In agreement with these findings, we demonstrate that induction of proinflammatory cytokines and type I interferon by fdsc‐αDEC was MYD88 mediated and TLR9 dependent. We also found that fdsc‐αDEC is delivered into LAMP‐1‐positive compartments and co‐localizes with TLR9. Thus, phage particles containing a single‐strand DNA genome rich in CpG motifs delivered via DEC‐205 are able to intercept and trigger the active TLR9 innate immune receptor into late endosome/lysosomes and to enhance the immunogenicity of the displayed antigenic determinants. These findings make fd bacteriophage a valuable tool for immunization without administering exogenous adjuvants. |
Databáze: | OpenAIRE |
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