title: Distinct Antigen Delivery Systems Induce Dendritic Cells' Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis.
abstract: Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells' maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated byIrf4,Ccl17, andCcr4over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells' polarization through the induction ofIl12b,Il12rb,Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis.
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, Via P. Castellino 111, 80131 Naples, Italy. valerio.costa@igb.cnr.it.
authors.forename: Valerio
authors.initials: V
authors.lastname: Costa
authors.affiliation: Dipartimento di Scienze Aziendali-Management & Innovation Systems/DISA-MIS, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy. d.righelli@na.iac.cnr.it.|Istituto per le Applicazioni del Calcolo, CNR, Via P. Castellino 111, 80131 Naples, Italy. d.righelli@na.iac.cnr.it.
authors.forename: Dario
authors.initials: D
authors.lastname: Righelli
authors.affiliation: Istituto per le Applicazioni del Calcolo, CNR, Via P. Castellino 111, 80131 Naples, Italy. francesco.russo.cib@gmail.com.|Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy. francesco.russo.cib@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Russo
authors.affiliation: Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy. p.deberardinis@ibp.cnr.it.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
authors.affiliation: Istituto per le Applicazioni del Calcolo, CNR, Via P. Castellino 111, 80131 Naples, Italy. c.angelini@iac.cnr.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy. l.dapice@ibp.cnr.it.
authors.forename: Luciana
authors.initials: L
authors.lastname: D'Apice
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D007109:Immunity / Q000235:genetics; D053858:Metabolic Networks and Pathways; D051379:Mice; D015203:Reproducibility of Results; D014158:Transcription, Genetic; D059467:Transcriptome; D014584:User-Computer Interface; D014612:Vaccines; D057188:Workflow
chemical_list: D000941:Antigens; D014612:Vaccines
keywords: RNA-Sequencing; dendritic cells; reproducible research; system vaccinology