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Int. J. Mol. Sci. 2017, 18(3), 494; doi:10.3390/ijms18030494

Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis

1
Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Via P. Castellino 111, 80131 Naples, Italy
2
Dipartimento di Scienze Aziendali—Management & Innovation Systems/DISA-MIS, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy
3
Istituto per le Applicazioni del Calcolo, CNR, Via P. Castellino 111, 80131 Naples, Italy
4
Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Chang Won Choi
Received: 5 January 2017 / Revised: 11 February 2017 / Accepted: 21 February 2017 / Published: 25 February 2017
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
View Full-Text   |   Download PDF [2552 KB, uploaded 25 February 2017]   |  

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 by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells’ polarization through the induction of Il12b, 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. View Full-Text
Keywords: system vaccinology; RNA-Sequencing; dendritic cells; reproducible research system vaccinology; RNA-Sequencing; dendritic cells; reproducible research
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Costa, V.; Righelli, D.; Russo, F.; De Berardinis, P.; Angelini, C.; D’Apice, L. Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis. Int. J. Mol. Sci. 2017, 18, 494.

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