Transcriptomic and Metabolic Responses to a Live-Attenuated <i>Francisella tularensis</i> Vaccine
Johannes B. Goll,
Shuzhao Li,
James L. Edwards,
Steven E. Bosinger,
Travis L. Jensen,
Yating Wang,
William F. Hooper,
Casey E. Gelber,
Katherine L. Sanders,
Evan J. Anderson,
Nadine Rouphael,
Muktha S. Natrajan,
Robert A. Johnson,
Patrick Sanz,
Daniel Hoft,
Mark J. Mulligan
Affiliations
Johannes B. Goll
The Emmes Company, Rockville, MD 20850, USA
Shuzhao Li
Departments of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
James L. Edwards
Department of Chemistry, Saint Louis University, St Louis, MO 63103, USA
Steven E. Bosinger
Yerkes National Primate Research Center, Secret Path, Atlanta, GA 30329, USA
Travis L. Jensen
The Emmes Company, Rockville, MD 20850, USA
Yating Wang
Departments of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
William F. Hooper
The Emmes Company, Rockville, MD 20850, USA
Casey E. Gelber
The Emmes Company, Rockville, MD 20850, USA
Katherine L. Sanders
Department of Chemistry, Saint Louis University, St Louis, MO 63103, USA
Evan J. Anderson
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Nadine Rouphael
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Muktha S. Natrajan
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Robert A. Johnson
Biomedical Advanced Research and Development Authority, U. S. Department of Health and Human Services, Washington, DC 20201, USA
Patrick Sanz
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
Daniel Hoft
Division of Infectious Diseases, Allergy and Immunology, Saint Louis University Health Sciences Center, St. Louis, MO 63104, USA
Mark J. Mulligan
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
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.
