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 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.

GeenaR: A Web Tool for Reproducible MALDI-TOF Analysis

“…The user can also re-execute the code on a local machine with minimal experience with the R language, such as suggested in Del Prete et al (2018) . Moreover, researchers can use the report as supplementary material in publications such as we did in the context of RNA-seq data analysis ( Costa et al, 2017 ). The reproducibility of the computational analysis constitutes one of the main advantages of GeenaR.…”

Easyreporting simplifies the implementation of Reproducible Research layers in R software

“…The RNA-seq data used in the example allows investigating the differences in CD8+ dendritic T-cells of the immune response of two different antibodies compared with control, see [19] for more details. We chose this illustrative example since it is well-known that the analysis of RNA-seq data can lack reproducibility [20].…”

The dawn of phage therapy

“…Host neutrophils and phages together fight against MDR P. aeruginosa in a mouse model of lung infection . Similarly, TLR9 and myeloid differentiation primary response 88 are essential for phage‐mediated antigen provision to dendritic cells followed by activation of T cells . Dendritic cells can engulf phage particles and present phage antigens to T cells resulting in the induction of cell‐mediated immunity and release of cytokines .…”