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Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status
The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among partic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627917/ https://www.ncbi.nlm.nih.gov/pubmed/28977039 http://dx.doi.org/10.1371/journal.pone.0185640 |
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author | Yu, Elaine A. John, Serene H. Tablante, Elizabeth C. King, Christine A. Kenneth, John Russell, David G. Mehta, Saurabh |
author_facet | Yu, Elaine A. John, Serene H. Tablante, Elizabeth C. King, Christine A. Kenneth, John Russell, David G. Mehta, Saurabh |
author_sort | Yu, Elaine A. |
collection | PubMed |
description | The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10), latent TB infection (LTBI, n = 10), and previous active TB disease (after successful treatment; PTBD, n = 10), relative to controls (n = 10). Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α). ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3, IL8) was similarly elevated, compared to individuals with PTBD. Our results demonstrated that samples from participants with ATBD and LTBI have distinct gene expression profiles in response to ex vivo M. tuberculosis infection. These findings indicate the value in further characterizing the peripheral responses to M. tuberculosis challenge as a route to defining immune correlates of disease status or outcome. |
format | Online Article Text |
id | pubmed-5627917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56279172017-10-20 Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status Yu, Elaine A. John, Serene H. Tablante, Elizabeth C. King, Christine A. Kenneth, John Russell, David G. Mehta, Saurabh PLoS One Research Article The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10), latent TB infection (LTBI, n = 10), and previous active TB disease (after successful treatment; PTBD, n = 10), relative to controls (n = 10). Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α). ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3, IL8) was similarly elevated, compared to individuals with PTBD. Our results demonstrated that samples from participants with ATBD and LTBI have distinct gene expression profiles in response to ex vivo M. tuberculosis infection. These findings indicate the value in further characterizing the peripheral responses to M. tuberculosis challenge as a route to defining immune correlates of disease status or outcome. Public Library of Science 2017-10-04 /pmc/articles/PMC5627917/ /pubmed/28977039 http://dx.doi.org/10.1371/journal.pone.0185640 Text en © 2017 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yu, Elaine A. John, Serene H. Tablante, Elizabeth C. King, Christine A. Kenneth, John Russell, David G. Mehta, Saurabh Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status |
title | Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status |
title_full | Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status |
title_fullStr | Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status |
title_full_unstemmed | Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status |
title_short | Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status |
title_sort | host transcriptional responses following ex vivo re-challenge with mycobacterium tuberculosis vary with disease status |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627917/ https://www.ncbi.nlm.nih.gov/pubmed/28977039 http://dx.doi.org/10.1371/journal.pone.0185640 |
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