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Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System for Intracellular Survival.

Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System for Intracellular Survival.
Author Information (click to view)

von Both U, Berk M, Agapow PM, Wright JD, Git A, Hamilton MS, Goldgof G, Siddiqui N, Bellos E, Wright VJ, Coin LJ, Newton SM, Levin M,


von Both U, Berk M, Agapow PM, Wright JD, Git A, Hamilton MS, Goldgof G, Siddiqui N, Bellos E, Wright VJ, Coin LJ, Newton SM, Levin M, (click to view)

von Both U, Berk M, Agapow PM, Wright JD, Git A, Hamilton MS, Goldgof G, Siddiqui N, Bellos E, Wright VJ, Coin LJ, Newton SM, Levin M,

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Scientific reports 2018 01 128(1) 661 doi 10.1038/s41598-017-18528-y
Abstract

Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation. To identify mechanisms underlying suppression of multiple immune genes we undertook epigenetic analyses. We identified significantly differentially expressed microRNAs with known targets in suppressed genes. In addition, after searching regions upstream of the start of transcription of suppressed genes for common sequence motifs, we discovered novel enriched composite sequence patterns, which corresponded to Alu repeat elements, transposable elements known to have wide ranging influences on gene expression. Our findings suggest that to survive within infected cells, mycobacteria exploit a complex immune "molecular off switch" controlled by both microRNAs and Alu regulatory elements.

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