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Tuberculosis (TB) is the cause of 2 million deaths each year, which is the second highest cause of mortality from a single infectious disease worldwide. Resistance of these organisms to drugs has emerged as an important health concern. Alternative approaches to the prevention and treatment of tuberculosis are therefore urgently needed. Despite the generation of robust host immune responses, Mycobacterium tuberculosis (M. tb) successfully evades host immunity and establishes a persistent infection. The mechanism(s) by which M. tuberculosis manages to persist in the face of potent host immune responses remain(s) incompletely understood. Here, we demonstrate that M. tb suppresses T-lymphocyte responses by recruiting mesenchymal stem cells (MSCs) to the site of infection. We found that MSCs infiltrated tissues in mice containing M. tb organisms and T lymphocytes. We further demonstrate that MSCs suppressed T-cell responses by producing nitric oxide. Our findings reveal a key role of MSCs in the capacity of M. tb to evade host immune responses and identify these cells as unique targets for therapeutic intervention in tuberculosis. immunosuppression | immune tolerance doi/ 10.1073/pnas.1007967107

To generate efficient vaccines and cures for Mycobacterium tuberculosis, we need a far better understanding of its modes of infection, persistence, and spreading. Host cell entry and the establishment of a replication niche are welt understood, but little is known about how tubercular mycobacteria exit host cells and disseminate the infection. Using the social amoeba Dictyostelium as a genetically tractable host for pathogenic mycobacteria, we discovered that M. tuberculosis and M. marinum, but not M. avium, are ejected from the cell through an actin-based structure, the ejectosome. This conserved nonlytic spreading mechanism requires a cytosketeton regulator from the host and an intact mycobacterial ESX-1 secretion system. This insight offers new directions for research into the spreading of tubercular mycobacteria infections in mammalian cells.

Recent studies have shown that fine structural modifications of Mycobacterium tuberculosis cell envelope lipids mediate host cell immune activation during infection. One such alteration in lipid structure is cis-cyclopropane modification [...]

Mycolic acids and structures attached to them constitute a major part of the protective envelope of Mycobacterium tuberculosis, and for this reason, their role in tuberculosis pathogenesis has been extensively [...]

In a 7-year population-based study in Malawi, we showed that Beijing genotype tuberculosis (TB) increased as a proportion of TB cases. All the Beijing genotype strains were fully drug sensitive. [...]

To the Editor: Mycobacterium tuberculosis (MTB) Beijing genotype is spread throughout the world, and the highest prevalence has been detected in Asia and Eurasia. In western Europe, the prevalence of [...]