Mycobacterium tuberculosis blocks phagolysosome maturation in alveolar macrophages of tuberculosis patients

Tuberculosis (TB) is an airborne dangerous disease caused by M. tuberculosis (Mtb) and characterized by a tight interplay between Mtb and host cells. Instead of being eliminated, Mtb demonstrates the remarkable ability to survive, replicate, and persist in human lungs on a long time. Studies of the mechanisms of Mtb survival within alveolar macrophages during TB infection are extremely important for the development of new vaccines and methods for TB treatment.Previously, we established the intravacuolar location of Mtb with different virulence, as single and in colonies, in alveolar macrophages of patients with pulmonary TB. Here, we analyzed the relationships between Mtb and TB patients’ alveolar macrophages in phagosomal compartments. In confocal fluorescence microscopy assay with the use of antibodies and other reagents, we determined that Mtb phagosomes can have the sings both the early (the presence of CD14 receptor and the lack of reactive oxygen species) and the late (the presence of iNOS) phagosomes. The lack of colocalization of the acidophilic LysoTracker probe and Mtb phagosomes was observed. Also, no colocalization of Mtb phagosomes with filamentous actin was identified. However, we detected numerous host cell vesicles with Mtb secreted products fused with lysosomes and filamentous actin. Therefore, alveolar macrophages retained their function to utilize vesicles with Mtb lipoarabinomannan, glycoprotein Ag 38, and ESAT-6 protein, but Mtb avoided host killing...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Tuberculosis Source Type: research