Phagocytosis and autophagy at the cross road.

COLOMBO, M. I.

Bourbon Ibirapuera Convention, São Paulo, SP, Brazil

Simposio; XV Meeting of the Brazilian Society for Cell Biology; 2010

In order to shelter from components of the host immune system, such as the complement system, numerous pathogens use as strategy the invasion of host cells. However, cells have developed powerful means to destroy invading pathogens via the generation of reactive oxygen species, modulation of essential cations and nutrients, and degradation by proteolytic enzymes. Thus, intracellular pathogens have developed sophisticated mechanisms to overcome host cell defenses and replicate successfully. One of the mechanisms employed by bacteria to evade the host innate immune response is to escape into the cytoplasm to avoid lysosomal killing. Other intracellular microorganisms stay inside the vacuolar phagosome, but hamper their maturation into phagolysosomes, thus guaranteeing the progression of the infectious process. A third strategy is to divert trafficking from the normal phagosomal pathway towards the autophagic pathway. Autophagy is a highly regulated and vital cellular process that involves rearrangement of subcellular membranes to sequester cytoplasmic portions and organelles. By fusion with lysosomes, the sequestered material is degraded and the molecules reused.  Several lines of evidence show that certain bacteria and viruses avoid or in contrast, actively subvert autophagy to promote their own replication.  We have studied some intracellular bacterial pathogens characterized by surviving and replicating into the host cell with different intracellular life styles such as Mycobacterium tuberculosis, M. marinum, Staphylococcus aureus. Several of these microbes manipulate the autophagic pathway at the molecular level as a strategy to establish persistent infection. However, transit through the autophagy pathway is not beneficial for most pathogens and autophagic events are critical cell defense mechanisms against invading microorganisms. Our results provide a novel perspective for understanding the importance of autophagy as a modulator of intracellular pathogens fate.