In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-01-28)
Abstract:
Every year, around two million people worldwide die from tuberculosis, a disease caused by the bacterium Mycobacterium tuberculosis (Mtb). The bacteria generally infect the lungs. In response, the immune system forms structures called granulomas that attempt to control and isolate the infecting pathogens. Granulomas consist of immune cells known as macrophages, which engulf the M. tuberculosis bacteria and isolate them in a cellular compartment where the bacteria either cannot grow or are killed. However, if a large number of macrophages in a granuloma die, the granuloma’s core liquefies and the structure is coughed up into the airways, from where M. tuberculosis bacteria are transmitted to other people. But how do the bacteria manage to cause the extensive death of the cells that are supposed to control the infection? By imaging M. tuberculosis in human macrophages using time-lapse microscopy, Mahamed et al. reveal that the bacteria break down macrophage control by serially killing macrophages. M. tuberculosis cells first clump together and ‘gang up’ on a macrophage, which engulfs the clump and dies because the bacteria overwhelm it. This does not kill the bacteria, and they rapidly grow inside the dead macrophage. The dead cell is then cleaned up by another macrophage. However, the increasing number of bacteria inside the dead macrophage means that the new macrophage is even more likely to die than the first one. Hence, the bacteria use dead macrophages as fuel to grow on and as bait to attract the next immune cell. Overall, Mahamed et al. show that once a clump of M. tuberculosis initiates death of a single macrophage, it may lead to serial killing of other macrophages and a loss of control over the infection. An important next step will be to understand how the initial clump of bacteria is allowed to form.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.22028.001
DOI:
10.7554/eLife.22028.002
DOI:
10.7554/eLife.22028.003
DOI:
10.7554/eLife.22028.004
DOI:
10.7554/eLife.22028.005
DOI:
10.7554/eLife.22028.006
DOI:
10.7554/eLife.22028.007
DOI:
10.7554/eLife.22028.008
DOI:
10.7554/eLife.22028.009
DOI:
10.7554/eLife.22028.010
DOI:
10.7554/eLife.22028.011
DOI:
10.7554/eLife.22028.012
DOI:
10.7554/eLife.22028.013
DOI:
10.7554/eLife.22028.014
DOI:
10.7554/eLife.22028.015
DOI:
10.7554/eLife.22028.016
DOI:
10.7554/eLife.22028.017
DOI:
10.7554/eLife.22028.018
DOI:
10.7554/eLife.22028.019
DOI:
10.7554/eLife.22028.020
DOI:
10.7554/eLife.22028.021
DOI:
10.7554/eLife.22028.022
DOI:
10.7554/eLife.22028.023
DOI:
10.7554/eLife.22028.024
DOI:
10.7554/eLife.22028.025
DOI:
10.7554/eLife.22028.026
DOI:
10.7554/eLife.22028.027
DOI:
10.7554/eLife.22028.028
DOI:
10.7554/eLife.22028.029
DOI:
10.7554/eLife.22028.030
DOI:
10.7554/eLife.22028.031
DOI:
10.7554/eLife.22028.032
DOI:
10.7554/eLife.22028.033
DOI:
10.7554/eLife.22028.034
DOI:
10.7554/eLife.22028.036
DOI:
10.7554/eLife.22028.037
DOI:
10.7554/eLife.22028.035
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
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