Manipulation of the immune system by the tubercle bacillus

29 December 2015

BPRC - 1. Manipulation of the immune system by the tubercle bacillus

Annually, TB kills about 1.5 million people. Improved diagnostics and tools to monitor treatment effects would significantly enhance effectiveness of TB therapies.

Mycobacterium tuberculosis, the bacterial agent that causes TB, typically settles in the lungs. This organ is not directly accessible, which complicates diagnostics and assessment of the effect of (experimental) treatment. It is known that TB has an effect on the so-called monocytes of the immune system. Scientists have now further investigated and unraveled some mechanisms that underly the effects of TB infection on this cell type.

The immune system is dedicated to eliminate pathogens. However, the tuberculous bacillus is well-equipped to evade immunity. In the present study researchers showed how TB infection manipulates a particular cell type of the immune system, CD16 + monocytes, to develop into type-II macrophages that support bacterial replication and pathogenic cascades. The mechanism of this type II polarisation of monocytes/macrophages mostly relied on interleukin-10/STAT3 signalling. Also on the basis of work and materials from BPRC’s preclinical studies, a positive correlation was found between the abundance of these immunomodulatory type-II macrofages and the severity of lung TB. In man (but not in non-human primates yet) the CD163 marker molecule from this CD16+ subset was more abundant in the serum of active TB disease patients. The study provides leads for possible therapeutic intervention and improved diagnostics in TB.

This study was published in the leading scientific magazine Cell Research (http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2015123a.html).