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

Significance To secure their colonization and survival, pathogens have evolved tactics to undermine host immune responses. Most particularly, Mycobacterium tuberculosis inhibits the activation of macrophages, one of whose roles is to recognize and kill invading microorganisms. Here, we used a library of M. tuberculosis mutants to infect macrophages and uncover molecular mechanisms by which the pathogen modulates the function of these immune cells. We 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.