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

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 languageEnglish (US)
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Apr 30 2018

Fingerprint

Dive into the research topics of 'Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages'. Together they form a unique fingerprint.

Cite this