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Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction

Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to ce...

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Autores principales: Teles, Rosane M. B., Lu, Jing, Tió-Coma, Maria, Goulart, Isabela M. B., Banu, Sayera, Hagge, Deanna, Bobosha, Kidist, Ottenhoff, Tom H. M., Pellegrini, Matteo, Geluk, Annemieke, Modlin, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805014/
https://www.ncbi.nlm.nih.gov/pubmed/31600201
http://dx.doi.org/10.1371/journal.pntd.0007764
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author Teles, Rosane M. B.
Lu, Jing
Tió-Coma, Maria
Goulart, Isabela M. B.
Banu, Sayera
Hagge, Deanna
Bobosha, Kidist
Ottenhoff, Tom H. M.
Pellegrini, Matteo
Geluk, Annemieke
Modlin, Robert L.
author_facet Teles, Rosane M. B.
Lu, Jing
Tió-Coma, Maria
Goulart, Isabela M. B.
Banu, Sayera
Hagge, Deanna
Bobosha, Kidist
Ottenhoff, Tom H. M.
Pellegrini, Matteo
Geluk, Annemieke
Modlin, Robert L.
author_sort Teles, Rosane M. B.
collection PubMed
description Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an ‘RR signature’ of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria.
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spelling pubmed-68050142019-11-02 Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction Teles, Rosane M. B. Lu, Jing Tió-Coma, Maria Goulart, Isabela M. B. Banu, Sayera Hagge, Deanna Bobosha, Kidist Ottenhoff, Tom H. M. Pellegrini, Matteo Geluk, Annemieke Modlin, Robert L. PLoS Negl Trop Dis Research Article Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an ‘RR signature’ of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria. Public Library of Science 2019-10-10 /pmc/articles/PMC6805014/ /pubmed/31600201 http://dx.doi.org/10.1371/journal.pntd.0007764 Text en © 2019 Teles 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
Teles, Rosane M. B.
Lu, Jing
Tió-Coma, Maria
Goulart, Isabela M. B.
Banu, Sayera
Hagge, Deanna
Bobosha, Kidist
Ottenhoff, Tom H. M.
Pellegrini, Matteo
Geluk, Annemieke
Modlin, Robert L.
Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
title Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
title_full Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
title_fullStr Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
title_full_unstemmed Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
title_short Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
title_sort identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805014/
https://www.ncbi.nlm.nih.gov/pubmed/31600201
http://dx.doi.org/10.1371/journal.pntd.0007764
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