Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum

Abstract The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to M...

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Autores principales:	Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05540afead234068a7e0b6a9d5e50ad4
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spelling	oai:doaj.org-article:05540afead234068a7e0b6a9d5e50ad42021-12-02T11:52:24ZActive nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum10.1038/s41598-017-06099-x2045-2322https://doaj.org/article/05540afead234068a7e0b6a9d5e50ad42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06099-xhttps://doaj.org/toc/2045-2322Abstract The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.Amy KenyonDaria GavriouchkinaJernej ZormanGiorgio NapolitaniVincenzo CerundoloTatjana Sauka-SpenglerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amy Kenyon Daria Gavriouchkina Jernej Zorman Giorgio Napolitani Vincenzo Cerundolo Tatjana Sauka-Spengler Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
description	Abstract The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.
format	article
author	Amy Kenyon Daria Gavriouchkina Jernej Zorman Giorgio Napolitani Vincenzo Cerundolo Tatjana Sauka-Spengler
author_facet	Amy Kenyon Daria Gavriouchkina Jernej Zorman Giorgio Napolitani Vincenzo Cerundolo Tatjana Sauka-Spengler
author_sort	Amy Kenyon
title	Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
title_short	Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
title_full	Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
title_fullStr	Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
title_full_unstemmed	Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum
title_sort	active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to mycobacterium marinum
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/05540afead234068a7e0b6a9d5e50ad4
work_keys_str_mv	AT amykenyon activenucleartranscriptomeanalysisrevealsinflammasomedependentmechanismforearlyneutrophilresponsetomycobacteriummarinum AT dariagavriouchkina activenucleartranscriptomeanalysisrevealsinflammasomedependentmechanismforearlyneutrophilresponsetomycobacteriummarinum AT jernejzorman activenucleartranscriptomeanalysisrevealsinflammasomedependentmechanismforearlyneutrophilresponsetomycobacteriummarinum AT giorgionapolitani activenucleartranscriptomeanalysisrevealsinflammasomedependentmechanismforearlyneutrophilresponsetomycobacteriummarinum AT vincenzocerundolo activenucleartranscriptomeanalysisrevealsinflammasomedependentmechanismforearlyneutrophilresponsetomycobacteriummarinum AT tatjanasaukaspengler activenucleartranscriptomeanalysisrevealsinflammasomedependentmechanismforearlyneutrophilresponsetomycobacteriummarinum
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Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum

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