Phagocytosis is the process by which cells engulf particles and microbial pathogens. The mechanism of the initial innate immune response by macrophages against intracellular pathogens involves phagocytosis, followed by killing. In higher eukaryotes, this process is predominantly the function of specialized ‘professional’ phagocytes.
During phagocytosis, the particle becomes enclosed by a membrane to form the phagosome. After phagosome formation, this organelle undergoes a series of dynamic fusion and fission events that modify the composition of its limiting membrane and its contents by interacting with components of the endocytic pathway. This process, referred to as phagosome maturation, provides the phagosome with degradative and microbicidal properties. In addition, microbial antigens are processed in phagosomes and directed to the plasma membrane associated to MHC I and II and CD1 molecules, to be presented to different subsets of lymphocytes. Therefore, the phagosome can be considered as an intracellular compartment that links the innate and adaptive immune systems.
The importance of phagocytosis in immunity is highlighted by the fact that different intracellular pathogens have learnt to subvert the normal phagosome maturation pathway for their own benefits. One of the best examples is Mycobacterium tuberculosis, the etiologic agent of tuberculosis.
According to the World Health Organization (WHO), tuberculosis causes over 2 million human deaths per year. In addition, approximately 8 to 10 million people are newly infected every year. It is estimated that every second someone in the world is newly infected with M. tuberculosis. The key event during M. tuberculosis infection is the ability of this pathogen to survive within phagosomes in macrophages. This capability is linked to the aptitude of the live pathogen to block phagosome maturation. Pathogenic mycobacteria survive within macrophages, whereas non-pathogenic mycobacteria are killed by macrophages. This means that somehow pathogenic mycobacteria block essential mechanisms of killing activated by non pathogenic-mycobacteria. Therefore, by studying how non-pathogenic mycobacteria are killed, it would be possible to identify the mechanisms of killing that are activated within macrophages. It is also likely that these mechanisms are the key targets that pathogenic mycobacteria subvert to survive. We have identified novel proteins involved in vesicular trafficking and possibly phago-lysosome fusion, during mycobacterium infection. These proteins are promising candidates for being involved in the lysosomal-mediated killing process, as well as in the molecular events linking innate and adaptive immune responses.