Autophagy in immunity against intracellular bacteria.
Autophagy is an innate immune defense mechanism against various intracellular bacterial pathogens, such as Salmonella enterica serovar Typhimurium (S. typhimurium), Listeria monocytogenes and Shigella flexneri. S. typhimurium uses type three secretion systems (T3SSs) to invade mammalian cells and replicate in Salmonella-containing vacuoles (SCVs). A small population of intracellular S. typhimurium is targeted by autophagy shortly after infection. Evidence suggests that these bacteria are present within SCVs that have been damaged by high levels of T3SS activity. Autophagy limits the growth of S. typhimurium in host cells. Therefore, autophagy can be considered to protect the cytosol of eukaryotic cells from bacterial colonization. L. monocytogenes secretes the pore-forming cytolysin listeriolysin O (LLO) to disrupt the phagosome and escape into the cytosol, where it acquires actin-based motility. Autophagy can target L. monocytogenes in the cytosol under specific experimental conditions. However, L. monocytogenes utilizes several virulence factors to evade being killed by the autophagy system. A newly appreciated population of L. monocytogenes undergoes slow growth in specialized vacuoles termed spacious Listeria-containing phagosomes (SLAPs), the formation of which requires bacterial LLO and host autophagy. In the cytosol, S. flexneri can also be a target for autophagy in the absence of a T3SS effector, IcsB, that normally impairs the interaction between Atg5 and wild-type bacteria. Therefore, autophagy can recognize intracellular bacteria in a variety of ways, leading to different fates for these bacteria in host cells. The inefficient autophagy of enteric bacteria in genetically compromised individuals may contribute to the pathogenesis of Crohn's disease.
Huang
Ju
J
Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Brumell
John H
JH
D000818:Animals; D001343:Autophagy / Q000276:immunology*; D004405:Dysentery, Bacillary / Q000276:immunology / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D010588:Phagosomes / Q000382:microbiology*; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology*