Tuberculosis: new aspects of an old disease

Abstract

Tuberculosis is an ancient infectious disease that remains a threat for public health around the world. Although the etiological agent as well as tuberculosis pathogenesis is well known, the molecular mechanisms underlying the host defense to the bacilli remain elusive. In this paper we focus on the innate immunity of this disease reviewing well-established and consensual mechanisms like Mycobacterium tuberculosis interference with phagosome maturation, less consensual mechanism like nitric oxide production, and new mechanisms, such as mycobacteria translocation to the cytosol, autophagy, and apoptosis/necrosis proposed mainly during the last decade.

Figure 1

Maturation process of pathogen-containing phagosomes. Diagram outlining the differences between endosome progression to lysosome (center), maturation of a phagosome harboring a live pathogen, for example, M. tuberculosis H37rv (left) and a phagosome harboring a dead pathogen (right). The fusion processes of phagosomes containing live/dead pathogens with compartments of the endosomal pathway are indicated by bold arrows. The traced arrows indicate inhibition of the fusion events between the phagosome harboring the live pathogen and the endocytic compartment. The diagram also illustrates the importance of two components of the cell's cytoskeleton in phagosome maturation. Actin is recruited to the phagocytic cup and might nucleate on the phagosome membrane during the maturation process. The microtubules, to which endocytic vesicles and phagosomes are thought to bind during the maturation process, are also represented. EE: early endossome; MVB: multivesicular bodies; LE: late endosome; LY: lysosome. Diagram adapted from [71].