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  • Title: Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine.
    Author: Goll JB, Li S, Edwards JL, Bosinger SE, Jensen TL, Wang Y, Hooper WF, Gelber CE, Sanders KL, Anderson EJ, Rouphael N, Natrajan MS, Johnson RA, Sanz P, Hoft D, Mulligan MJ.
    Journal: Vaccines (Basel); 2020 Jul 24; 8(3):. PubMed ID: 32722194.
    Abstract:
    The immune response to live-attenuated Francisella tularensis vaccine and its host evasion mechanisms are incompletely understood. Using RNA-Seq and LC-MS on samples collected pre-vaccination and at days 1, 2, 7, and 14 post-vaccination, we identified differentially expressed genes in PBMCs, metabolites in serum, enriched pathways, and metabolites that correlated with T cell and B cell responses, or gene expression modules. While an early activation of interferon α/β signaling was observed, several innate immune signaling pathways including TLR, TNF, NF-κB, and NOD-like receptor signaling and key inflammatory cytokines such as Il-1α, Il-1β, and TNF typically activated following infection were suppressed. The NF-κB pathway was the most impacted and the likely route of attack. Plasma cells, immunoglobulin, and B cell signatures were evident by day 7. MHC I antigen presentation was more actively up-regulated first followed by MHC II which coincided with the emergence of humoral immune signatures. Metabolomics analysis showed that glycolysis and TCA cycle-related metabolites were perturbed including a decline in pyruvate. Correlation networks that provide hypotheses on the interplay between changes in innate immune, T cell, and B cell gene expression signatures and metabolites are provided. Results demonstrate the utility of transcriptomics and metabolomics for better understanding molecular mechanisms of vaccine response and potential host-pathogen interactions.
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