Figure 2.

How autophagy and LC3-assisted phagocytosis defend cells against infection. Synergistic lines of defence prevent the entry of pathogens into the cytosol of host cells. (a) LC3-assisted phagocytosis is triggered by Toll-like receptors (TLRs) and potentially other pattern recognition receptors (PRRs) in response to microorganisms that are taken up by phagocytosis or that have actively invaded nonphagocytic cells. LC3-assisted phagocytosis requires a subset of autophagy genes for the labelling of phagosomes with ATG8/LC3, which promotes their lysosomal delivery and the efficient killing of vesicular pathogens. (b) Damage to the limiting membrane of the pathogen-containing vesicle, either accidental or caused by pathogens attempting to escape from the vesicle, exposes the cytosol to glycans previously hidden inside the vesicle. (c) Cytosol-accessible glycans are detected by the danger receptor galectin-8, which, by recruiting the cargo receptor NDP52 (nuclear dot protein 52), triggers autophagy. (d) Pathogens having escaped galectin-8-induced autophagy are met by yet another layer of PRRs in the cytosol. (e) A yet-to-be-identified E3 ubiquitin ligase causes the ubiquitin-coating of invading bacteria. It remains to be established whether this ligase only targets membrane-associated or also free-floating bacteria, whether it is a PRR, and also whether its substrate is of bacterial or host origin. (f) Ubiquitin-coated bacteria are targeted for autophagy by three apparently non-redundant cargo receptors, that is, NDP52, p62, and optineurin.