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Sci Rep. 2018 Apr 30;8(1):6758. doi: 10.1038/s41598-018-24509-6.

Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages.

Author information

1
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
2
Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
3
Massey University, Institute of Natural and Mathematical Sciences, Auckland, New Zealand.
4
RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
5
King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Thuwal, Saudi Arabia.
6
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town component, Cape Town, 7925, South Africa.
7
University of Cape Town, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
8
Riken Preventive Medicine and Diagnosis Innovation Program (PMI), 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
9
Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Subiaco, Subiaco, 6008, Western Australia, Australia.
10
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town component, Cape Town, 7925, South Africa. frank.brombacher@icgeb.org.
11
University of Cape Town, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa. frank.brombacher@icgeb.org.
12
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. harukazu@gsc.riken.jp.
13
Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. harukazu@gsc.riken.jp.
14
RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. harukazu@gsc.riken.jp.

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.

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