Antigen delivery by filamentous bacteriophage fd displaying an anti‐ DEC ‐205 single‐chain variable fragment confers adjuvanticity by triggering a TLR 9‐mediated immune response

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 mechanism...

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Bibliographic Details
Published in:EMBO molecular medicine 2015-07, Vol.7 (7), p.973-988
Main Authors: 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
Format: Article
Language:English
Subjects:
Adjuvanticity
Adjuvants
Antigenic determinants
Antigens
Bioinformatics
CD8 antigen
CpG islands
Cytokines
Dendritic cells
Experiments
Genomes
Immunization
Immunogenicity
Immunoglobulins
Inflammation
Innate immunity
Interferon
Lymphocytes
Lysosomes
MyD88 protein
Peptides
Phages
Ribonucleic acid
RNA
TLR9 protein
Toll-like receptors
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Summary: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.
ISSN:1757-4676
1757-4684
DOI:10.15252/emmm.201404525