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Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis 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, metabol...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563297/ https://www.ncbi.nlm.nih.gov/pubmed/32722194 http://dx.doi.org/10.3390/vaccines8030412 |
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author | Goll, Johannes B. Li, Shuzhao Edwards, James L. Bosinger, Steven E. Jensen, Travis L. Wang, Yating Hooper, William F. Gelber, Casey E. Sanders, Katherine L. Anderson, Evan J. Rouphael, Nadine Natrajan, Muktha S. Johnson, Robert A. Sanz, Patrick Hoft, Daniel Mulligan, Mark J. |
author_facet | Goll, Johannes B. Li, Shuzhao Edwards, James L. Bosinger, Steven E. Jensen, Travis L. Wang, Yating Hooper, William F. Gelber, Casey E. Sanders, Katherine L. Anderson, Evan J. Rouphael, Nadine Natrajan, Muktha S. Johnson, Robert A. Sanz, Patrick Hoft, Daniel Mulligan, Mark J. |
author_sort | Goll, Johannes B. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7563297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75632972020-10-27 Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine Goll, Johannes B. Li, Shuzhao Edwards, James L. Bosinger, Steven E. Jensen, Travis L. Wang, Yating Hooper, William F. Gelber, Casey E. Sanders, Katherine L. Anderson, Evan J. Rouphael, Nadine Natrajan, Muktha S. Johnson, Robert A. Sanz, Patrick Hoft, Daniel Mulligan, Mark J. Vaccines (Basel) Article 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. MDPI 2020-07-24 /pmc/articles/PMC7563297/ /pubmed/32722194 http://dx.doi.org/10.3390/vaccines8030412 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Goll, Johannes B. Li, Shuzhao Edwards, James L. Bosinger, Steven E. Jensen, Travis L. Wang, Yating Hooper, William F. Gelber, Casey E. Sanders, Katherine L. Anderson, Evan J. Rouphael, Nadine Natrajan, Muktha S. Johnson, Robert A. Sanz, Patrick Hoft, Daniel Mulligan, Mark J. Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine |
title | Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine |
title_full | Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine |
title_fullStr | Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine |
title_full_unstemmed | Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine |
title_short | Transcriptomic and Metabolic Responses to a Live-Attenuated Francisella tularensis Vaccine |
title_sort | transcriptomic and metabolic responses to a live-attenuated francisella tularensis vaccine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563297/ https://www.ncbi.nlm.nih.gov/pubmed/32722194 http://dx.doi.org/10.3390/vaccines8030412 |
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