Autophagy in Immunity Against Intracellular Bacteria

Abstract

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.

A role for Atg8–PE deconjugation in autophagosome biogenesis

“…5 Autophagy was first identified in yeast as a starvation response essential for overcoming conditions of nutrient deprivation; however, in multicellular organisms, aside from its role in cellular homeostasis, autophagy is required for processes as diverse as the removal of protein aggregates and damaged or superfluous organelles, development and cellular remodeling, and immunity. [6][7][8] Indeed, defects in autophagy are associated with various diseases, such as cancer, gastrointestinal disorders, and neurodegeneration. [9][10][11] Interestingly, even though the role of autophagy seems to have significantly diverged in multicellular organisms, the core components of the autophagy machinery are evolutionarily conserved from yeast to human.…”

The Role of Autophagy during Group B Streptococcus Infection of Blood-Brain Barrier Endothelium

“…LC3 is conjugated to phosphatidylethanolamine, a lipid constituent of plasma membranes, by the ATG5-ATG12-ATG16L1 complex to allow for autophagosome expansion (19). Recently, antimicrobial autophagy, a selective type of autophagy also known as xenophagy, has emerged as a potent host defense mechanism against intracellular bacterial and viral pathogens (17,20). Several pathogenic bacteria such as Salmonella enterica serovar Typhimurium (Salmonella typhimurium), Listeria monocytogenes, Shigella flexneri, and group A Streptococcus (GAS) have been shown to activate the autophagic pathway (21)(22)(23).…”

Human Rhinovirus 2 Induces the Autophagic Pathway and Replicates More Efficiently in Autophagic Cells

“…The relationship between autophagy and bacterial and viral pathogens varies widely, from inhibiting to promoting pathogen growth (8,16,21). For example, autophagy is part of the antiviral defense against the negative-strand RNA virus vesicular stomatitis virus (25).…”