Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine
07/2020
Journal Article
Authors:
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.
Volume:
8
Pagination:
3
Journal:
Vaccines (Basel)
PMID:
32722194
URL:
https://www.ncbi.nlm.nih.gov/pubmed/32722194
Keywords:
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
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 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.
