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Mycobacterium tuberculosis plays hide-and-seek with the immune system

To secure their colonization and survival, pathogens have evolved tactics to undermine host immune responses. Better understanding pathogen invasion strategies is key to develop appropriate preventive or therapeutic tools. Scientists from the team "Immunomodulation by Mycobacterial Lipids and Glycoconjugates" at the Institute of Pharmacology and Structural Biology (IPBS  - CNRS/Université Toulouse III - Paul Sabatier) have uncovered a molecular mechanism by which the tuberculosis bacillus escapes detection by the innate immune system. This study is published in the Proceedings of the National Academy of Sciences of the USA, on October 2 2017.

 

Mycobacterium tuberculosis, the causative agent of human tuberculosis, is a bacterial pathogen that has adapted to subvert the function of macrophages, whose one of the roles is to recognize and kill invading microorganisms. In the present study, the scientists used a library of M. tuberculosis mutants to infect macrophages and decipher molecular mechanisms by which the pathogen modulates the function of these immune cells. They found that M. tuberculosis produces cell envelope glycolipids that are antagonists of a macrophage receptor, named TLR2, which is dedicated to the recognition of pathogens, thereby preventing its efficient recognition by the immune system.

 

Read the Press release (in French)

 

Reference

Landry Blanc,  Martine Gilleron, Jacques Prandi, Ok-ryul Song, Mi-Seon Jang, Brigitte Gicquel, Daniel Drocourt, Olivier Neyrolles, Priscille Brodin, Gérard Tiraby, Alain Vercellone & Jérôme Nigou (2017) Mycobacterium tuberculosis inhibits human innate immune responses via the production of TLR2 antagonist glycolipids. PNAS, Published ahead of print October 2, 2017 doi:10.1073/pnas.1707840114
 

Contact Jérôme Nigou (jerome.nigou@ipbs.fr)

 

This work was performed in collaboration with the Centre d'Infection et d'Immunité de Lille (CIIL), the Pasteur Institutes from Paris and Korea, and the biotech company InvivoGen (Toulouse).

 

Figure PNAS Nigou

 

Mycobacterium tuberculosis inhibits human innate immune responses via the production of TLR2 antagonist glycolipids.

TLR2 is pattern recognition receptor that heterodimerizes with TLR1 or TLR6 to recognize bacterial lipoproteins. It triggers an intracellular signaling pathway that leads to the activation of the transcription factor NF-κB and the production of pro-inflammatory cytokines, required to mount an efficient immune response against invading microorganisms. However, the pathogenic bacterium M. tuberculosis produces surface glycolipids at its cell envelope, named sulfoglycolipids, which are competitive inhibitors of TLR2/TLR1 and TLR2/TLR6 heterodimers.

©Jérôme Nigou & Martine Gilleron