Autophagy and bacterial infectious diseases

Abstract

Autophagy is a housekeeping process that maintains cellular homeostasis through recycling of nutrients and degradation of damaged or aged cytoplasmic constituents. Over the past several years, accumulating evidence has suggested that autophagy can function as an intracellular innate defense pathway in response to infection with a variety of bacteria and viruses. Autophagy plays a role as a specialized immunologic effector and regulates innate immunity to exert antimicrobial defense mechanisms. Numerous bacterial pathogens have developed the ability to invade host cells or to subvert host autophagy to establish a persistent infection. In this review, we have summarized the recent advances in our understanding of the interaction between antibacterial autophagy (xenophagy) and different bacterial pathogens.

Figure 1

The role of autophagy in control of innate immunity and the survival mechanisms of intracellular bacteria. Various intracellular bacteria are internalized by phagocytes; these survive in the cytosol or phagosome through various strategies. (1) First, some bacteria are able to escape from the phagosome by secreting factors and replicating in the host cytoplasm (left panel). When autophagy is induced, Listeria monocytogenes and Rickettsia conorii present in the cytoplasm are captured by the autophagosomal membrane and degraded by the autolysosome; however, Shigella flexneri has the ability to avoid import into the autophagosome. (2) Second, some bacteria reside in the phagosomal compartment (right panel). Upon autophagy activation, phagosomes containing Mycobacterium tuberculosis are caught by the autophagic vacuole and then degraded by fusion with the lysosome. In contrast, Brucella abortus and Legionella pneumophila can inhibit autophagosome maturation through inhibition of lysosome fusion, allowing the pathogen to survive and replicate.