Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

Abstract Mycobacterium tuberculosis (Mtb) infection reveals complex and dynamic host-pathogen interactions, leading to host protection or pathogenesis. Using a unique transcriptome technology (CAGE), we investigated the promoter-based transcriptional landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimula...

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Autores principales:	Sugata Roy, Sebastian Schmeier, Bogumil Kaczkowski, Erik Arner, Tanvir Alam, Mumin Ozturk, Ousman Tamgue, Suraj P. Parihar, Hideya Kawaji, Masayoshi Itoh, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair R. R. Forrest, Reto Guler, Vladimir B. Bajic, Frank Brombacher, Harukazu Suzuki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b734966dbbf4f9c900cb69c6e6dbf5b
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spelling	oai:doaj.org-article:5b734966dbbf4f9c900cb69c6e6dbf5b2021-12-02T16:08:27ZTranscriptional landscape of Mycobacterium tuberculosis infection in macrophages10.1038/s41598-018-24509-62045-2322https://doaj.org/article/5b734966dbbf4f9c900cb69c6e6dbf5b2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24509-6https://doaj.org/toc/2045-2322Abstract Mycobacterium tuberculosis (Mtb) infection reveals complex and dynamic host-pathogen interactions, leading to host protection or pathogenesis. Using a unique transcriptome technology (CAGE), we investigated the promoter-based transcriptional landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene Ontology enrichment analysis for Mtb-induced differentially expressed genes revealed various terms, related to host-protection and inflammation, enriched in up-regulated genes. On the other hand, terms related to dis-regulation of cellular functions were enriched in down-regulated genes. Differential expression analysis revealed known as well as novel transcription factor genes in Mtb infection, many of them significantly down-regulated. IFNγ or IL-4/IL-13 pre-stimulation induce additional differentially expressed genes in Mtb-infected macrophages. Cluster analysis uncovered significant numbers, prolonging their expressional changes. Furthermore, Mtb infection augmented cytokine-mediated M1 and M2 pre-activations. In addition, we identified unique transcriptional features of Mtb-mediated differentially expressed lncRNAs. In summary we provide a comprehensive in depth gene expression/regulation profile in Mtb-infected macrophages, an important step forward for a better understanding of host-pathogen interaction dynamics in Mtb infection.Sugata RoySebastian SchmeierBogumil KaczkowskiErik ArnerTanvir AlamMumin OzturkOusman TamgueSuraj P. PariharHideya KawajiMasayoshi ItohTimo LassmannPiero CarninciYoshihide HayashizakiAlistair R. R. ForrestReto GulerVladimir B. BajicFrank BrombacherHarukazu SuzukiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sugata Roy Sebastian Schmeier Bogumil Kaczkowski Erik Arner Tanvir Alam Mumin Ozturk Ousman Tamgue Suraj P. Parihar Hideya Kawaji Masayoshi Itoh Timo Lassmann Piero Carninci Yoshihide Hayashizaki Alistair R. R. Forrest Reto Guler Vladimir B. Bajic Frank Brombacher Harukazu Suzuki Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
description	Abstract Mycobacterium tuberculosis (Mtb) infection reveals complex and dynamic host-pathogen interactions, leading to host protection or pathogenesis. Using a unique transcriptome technology (CAGE), we investigated the promoter-based transcriptional landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene Ontology enrichment analysis for Mtb-induced differentially expressed genes revealed various terms, related to host-protection and inflammation, enriched in up-regulated genes. On the other hand, terms related to dis-regulation of cellular functions were enriched in down-regulated genes. Differential expression analysis revealed known as well as novel transcription factor genes in Mtb infection, many of them significantly down-regulated. IFNγ or IL-4/IL-13 pre-stimulation induce additional differentially expressed genes in Mtb-infected macrophages. Cluster analysis uncovered significant numbers, prolonging their expressional changes. Furthermore, Mtb infection augmented cytokine-mediated M1 and M2 pre-activations. In addition, we identified unique transcriptional features of Mtb-mediated differentially expressed lncRNAs. In summary we provide a comprehensive in depth gene expression/regulation profile in Mtb-infected macrophages, an important step forward for a better understanding of host-pathogen interaction dynamics in Mtb infection.
format	article
author	Sugata Roy Sebastian Schmeier Bogumil Kaczkowski Erik Arner Tanvir Alam Mumin Ozturk Ousman Tamgue Suraj P. Parihar Hideya Kawaji Masayoshi Itoh Timo Lassmann Piero Carninci Yoshihide Hayashizaki Alistair R. R. Forrest Reto Guler Vladimir B. Bajic Frank Brombacher Harukazu Suzuki
author_facet	Sugata Roy Sebastian Schmeier Bogumil Kaczkowski Erik Arner Tanvir Alam Mumin Ozturk Ousman Tamgue Suraj P. Parihar Hideya Kawaji Masayoshi Itoh Timo Lassmann Piero Carninci Yoshihide Hayashizaki Alistair R. R. Forrest Reto Guler Vladimir B. Bajic Frank Brombacher Harukazu Suzuki
author_sort	Sugata Roy
title	Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
title_short	Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
title_full	Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
title_fullStr	Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
title_full_unstemmed	Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
title_sort	transcriptional landscape of mycobacterium tuberculosis infection in macrophages
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5b734966dbbf4f9c900cb69c6e6dbf5b
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Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

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