Mycobacterium tuberculosis Exploits a Molecular OffSwitch of the Immune System for Intracellular Survival
Ulrich von Both, Maurice Berk, Paul-Michael Agapow, Joseph D Wright, Anna Git, Melissa Shea Hamilton, Greg Goldgof, Nazneen Siddiqui, Evangelos Bellos, Victoria J Wright, Lachlan J Coin, Sandra M Newton, Michael Levin
SCIENTIFIC REPORTS | NATURE RESEARCH | Published : 2018
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 mu..View full abstract
We thank: Ming-Shi Li for manifold practical advice to U.V.B., Jayne Dennis (St. George's Hospital Medical school) for help with Illumina arrays; Saranya Sridhar (Imperial College London) for assisting in designing the FAGS panel; Theodoros Xenakis and Charles Mein at The Genome Centre, Queen Mary University of London for running the methylation arrays; Simon Waddell for use of publicly available macrophage gene expression data; Tim Bailey for help with motif searches using MEME, Carlyn Zwarenstein for drawing and illustration of Fig. 1; all blood donors at Imperial College London. This work has been supported by a European Society of Paediatric Infectious Diseases (ESPID) Research Fellowship awarded to U.V.B., a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Research Grant awarded to U.V.B. and two Elsie Widdowson fellowships of Imperial College London awarded to S.M.N. M.L. was supported by an NIHR senior investigator award.