Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection

Detalhes bibliográficos
Autor(a) principal: Araujo, Leonardo Silva de
Data de Publicação: 2019
Outros Autores: Ribeiro-Alves, Marcelo, Leal-Calvo, Thyago, Leung, Janaína, Durán, Verónica, Samir, Mohamed, Talbot, Steven, Tallam, Aravind, Mello, Fernanda Carvalho de Queiroz, Geffers, Robert, Saad, Maria Helena Féres, Pessler, Frank
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/37965
Resumo: Marcelo Ribeiro Alves. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
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spelling Araujo, Leonardo Silva deRibeiro-Alves, MarceloLeal-Calvo, ThyagoLeung, JanaínaDurán, VerónicaSamir, MohamedTalbot, StevenTallam, AravindMello, Fernanda Carvalho de QueirozGeffers, RobertSaad, Maria Helena FéresPessler, Frank2019-12-16T14:15:20Z2019-12-16T14:15:20Z2019ARAUJO, Leonardo Silva de et al. Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection. mBio, v. 10, n. 6, p. 1-23, 2019.https://www.arca.fiocruz.br/handle/icict/3796510.1128/mBio.01037-192150-7511)Marcelo Ribeiro Alves. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Helmholtz Centre for Infection Research. Braunschweig, Germany.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Federal University of Rio de Janeiro. Thoracic Diseases Institute. Rio de Janeiro, RJ, Brazil.TWINCORE Centre for Experimental and Clinical Infection Research. Institute for Experimental Infection Research. Hannover, Germany.TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany / Zagazig University. Faculty of Veterinary Medicine. Department of Zoonoses. Zagazig, Egypt.TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany / Hannover Medical School. Institute for Laboratory Animal Science. Hannover, Germany.TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany.Federal University of Rio de Janeiro. Thoracic Diseases Institute. Rio de Janeiro, RJ, Brazil.Helmholtz Centre for Infection Research. Braunschweig, Germany.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany / Helmholtz Centre for Infection Research. Braunschweig, Germany / Centre for Individualised Infection Medicine, Hannover, Germany.In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTBI treatment. Logistic regression identified the combination of 4 sncRNA (let-7a-5p, miR-589-5p, miR-196b-5p, and SNORD104) as a highly sensitive (100%) classifier to discriminate TB from all non-TB groups. Notably, it reclassified 8 presumed LTBI cases as TB cases, 5 of which turned out to have features of Mycobacterium tuberculosis infection on chest radiographs. SNORD104 expression decreased during M. tuberculosis infection of primary human peripheral blood mononuclear cells (PBMC) and M2-like (P = 0.03) but not M1-like (P = 0.31) macrophages, suggesting that its downregulation in peripheral blood in TB is biologically relevant. Taken together, the results demonstrate that snoRNA and piRNA should be considered in addition to miRNA as biomarkers and pathogenesis factors in the various stages of TB.IMPORTANCE Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured expression changes in the four major classes of small noncoding RNAs in blood samples from patients with different stages of TB infection. We found that, in addition to miRNAs (which are known to be highly regulated in blood cells from TB patients), expression of piRNA and snoRNA is greatly altered in both latent and active TB, yielding promising biomarkers. Even though the functions of many sncRNA other than miRNA are still poorly understood, our results strongly suggest that at least piRNA and snoRNA populations may represent hitherto underappreciated players in the different stages of TB infection.engAmerican Society for MicrobiologyReprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBiomarkersBiosignaturemiRNAIncipient tuberculosispiRNARNAsnRNAsncRNAsnoRNASubclinical tuberculosisTranscriptomeTuberculosisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
title Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
spellingShingle Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
Araujo, Leonardo Silva de
Biomarkers
Biosignature
miRNA
Incipient tuberculosis
piRNA
RNA
snRNA
sncRNA
snoRNA
Subclinical tuberculosis
Transcriptome
Tuberculosis
title_short Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
title_full Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
title_fullStr Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
title_full_unstemmed Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
title_sort Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection
author Araujo, Leonardo Silva de
author_facet Araujo, Leonardo Silva de
Ribeiro-Alves, Marcelo
Leal-Calvo, Thyago
Leung, Janaína
Durán, Verónica
Samir, Mohamed
Talbot, Steven
Tallam, Aravind
Mello, Fernanda Carvalho de Queiroz
Geffers, Robert
Saad, Maria Helena Féres
Pessler, Frank
author_role author
author2 Ribeiro-Alves, Marcelo
Leal-Calvo, Thyago
Leung, Janaína
Durán, Verónica
Samir, Mohamed
Talbot, Steven
Tallam, Aravind
Mello, Fernanda Carvalho de Queiroz
Geffers, Robert
Saad, Maria Helena Féres
Pessler, Frank
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Araujo, Leonardo Silva de
Ribeiro-Alves, Marcelo
Leal-Calvo, Thyago
Leung, Janaína
Durán, Verónica
Samir, Mohamed
Talbot, Steven
Tallam, Aravind
Mello, Fernanda Carvalho de Queiroz
Geffers, Robert
Saad, Maria Helena Féres
Pessler, Frank
dc.subject.en.pt_BR.fl_str_mv Biomarkers
Biosignature
miRNA
Incipient tuberculosis
piRNA
RNA
snRNA
sncRNA
snoRNA
Subclinical tuberculosis
Transcriptome
Tuberculosis
topic Biomarkers
Biosignature
miRNA
Incipient tuberculosis
piRNA
RNA
snRNA
sncRNA
snoRNA
Subclinical tuberculosis
Transcriptome
Tuberculosis
description Marcelo Ribeiro Alves. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-12-16T14:15:20Z
dc.date.available.fl_str_mv 2019-12-16T14:15:20Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv ARAUJO, Leonardo Silva de et al. Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection. mBio, v. 10, n. 6, p. 1-23, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/37965
dc.identifier.doi.none.fl_str_mv 10.1128/mBio.01037-19
dc.identifier.eissn.none.fl_str_mv 2150-7511)
identifier_str_mv ARAUJO, Leonardo Silva de et al. Reprogramming of small noncoding RNA populations in peripheral blood reveals host biomarkers for latent and active Mycobacterium tuberculosis infection. mBio, v. 10, n. 6, p. 1-23, 2019.
10.1128/mBio.01037-19
2150-7511)
url https://www.arca.fiocruz.br/handle/icict/37965
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/37965/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/37965/2/ve_Araujo_Leonardo_etal_INI_2019.pdf
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