Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response

作者：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^*

来源：EMBO Molecular Medicine, 2015, 7(7): 973-988.

DOI：10.15252/emmm.201404525

• antigen delivery
• DEC-205
• dendritic cells
• filamentous bacteriophage
• TLR9

Filamentous bacteriophage fd particles delivering antigenic determinants via DEC-205 (fdsc-DEC) 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-DEC was MYD88 mediated and TLR9 dependent. We also found that fdsc-DEC 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.

• 出版日期2015-7