Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

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

doi:10.1038/s41598-018-24509-6

Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

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.

Original language	English
Article number	6758
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-24509-6
Publication status	Published - 1 Dec 2018
Externally published	Yes

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Roy, S., Schmeier, S., Kaczkowski, B., Arner, E., Alam, T., Ozturk, M., Tamgue, O., Parihar, S. P., Kawaji, H., Itoh, M., Lassmann, T., Carninci, P., Hayashizaki, Y., Forrest, A. R. R., Guler, R., Bajic, V. B., Brombacher, F., & Suzuki, H. (2018). Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages. Scientific Reports, 8(1), Article 6758. https://doi.org/10.1038/s41598-018-24509-6

@article{b0493c0b96dd467cb2254ca5e5c16e3b,

title = "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) 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.",

author = "Sugata Roy and Sebastian Schmeier and Bogumil Kaczkowski and Erik Arner and Tanvir Alam and Mumin Ozturk and Ousman Tamgue and Parihar, \{Suraj P.\} and Hideya Kawaji and Masayoshi Itoh and Timo Lassmann and Piero Carninci and Yoshihide Hayashizaki and Forrest, \{Alistair R.R.\} and Reto Guler and Bajic, \{Vladimir B.\} and Frank Brombacher and Harukazu Suzuki",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-24509-6",

language = "English",

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Roy, S, Schmeier, S, Kaczkowski, B, Arner, E, Alam, T, Ozturk, M, Tamgue, O, Parihar, SP, Kawaji, H, Itoh, M, Lassmann, T, Carninci, P, Hayashizaki, Y, Forrest, ARR, Guler, R, Bajic, VB, Brombacher, F & Suzuki, H 2018, 'Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages', Scientific Reports, vol. 8, no. 1, 6758. https://doi.org/10.1038/s41598-018-24509-6

TY - JOUR

T1 - Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

AU - Roy, Sugata

AU - Schmeier, Sebastian

AU - Kaczkowski, Bogumil

AU - Arner, Erik

AU - Alam, Tanvir

AU - Ozturk, Mumin

AU - Tamgue, Ousman

AU - Parihar, Suraj P.

AU - Kawaji, Hideya

AU - Itoh, Masayoshi

AU - Lassmann, Timo

AU - Carninci, Piero

AU - Hayashizaki, Yoshihide

AU - Forrest, Alistair R.R.

AU - Guler, Reto

AU - Bajic, Vladimir B.

AU - Brombacher, Frank

AU - Suzuki, Harukazu

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85046375642

U2 - 10.1038/s41598-018-24509-6

DO - 10.1038/s41598-018-24509-6

M3 - Article

C2 - 29712924

AN - SCOPUS:85046375642

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 6758

ER -

Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

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