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Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine


Journal Article

Goll, J. B.; Li, S.; Edwards, J. L.; Bosinger, S. E.; Jensen, T. L.; Wang, Y.; Hooper, W. F.; Gelber, C. E.; Sanders, K. L.; Anderson, E. J.; Rouphael, N.; Natrajan, M. S.; Johnson, R. A.; Sanz, P.; Hoft, D. ; Mulligan, M. J.



Vaccines (Basel)




Dvc-lvs Francisella tularenis vaccine Francisella tularensis Lc-ms NF-kappaB NOD-like receptor RNA-Seq Tlr Tnf human immune response innate immune signaling interferon alpha/beta signaling metabolomics suppression of immune response tularemia vaccine

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 alpha/beta signaling was observed, several innate immune signaling pathways including TLR, TNF, NF-kappaB, and NOD-like receptor signaling and key inflammatory cytokines such as Il-1alpha, Il-1beta, and TNF typically activated following infection were suppressed. The NF-kappaB 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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