title: Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response.
abstract: 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.
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Sartorius
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: D'Apice
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trovato
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy.
authors.forename: Fausta
authors.initials: F
authors.lastname: Cuccaro
authors.affiliation: Institute of Genetics and Biophysics A. Buzzati-Traverso, National Council of Research, Naples, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Costa
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: De Leo
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy.
authors.forename: Vincenzo Manuel
authors.initials: VM
authors.lastname: Marzullo
authors.affiliation: Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Messina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Biondo
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy Institute of Food Science, National Council of Research, Avellino, Italy.
authors.forename: Sabato
authors.initials: S
authors.lastname: D'Auria
authors.affiliation: Telethon Institute of Genetics and Medicine, Pozzuoli (NA), Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Matteis
authors.affiliation: Institute of Genetics and Biophysics A. Buzzati-Traverso, National Council of Research, Naples, Italy Department of Science and Technology, University Parthenope of Naples, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ciccodicola
authors.affiliation: Institute of Protein Biochemistry, National Council of Research, Naples, Italy p.deberardinis@ibp.cnr.it.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D061505:Cell Surface Display Techniques; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004337:Drug Carriers; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D017912:Inovirus / Q000235:genetics*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D057127:Single-Chain Antibodies / Q000276:immunology / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D015703:Antigens, CD; C093569:DEC-205 receptor; D004337:Drug Carriers; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D057127:Single-Chain Antibodies; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: DEC‐205; TLR9; antigen delivery; dendritic cells; filamentous bacteriophage