Phagolysosomal cargo degradation

Once a phagosome has matured into a phagolysosome, acid hydrolases digest the engulfed particle and transporters in the phagolysosomal membrane return the products to the cytosol. DNase II finishes digesting the DNA of engulfed cells; cathepsins digest proteins; in amoebae that eat bacteria, lysozymes break down the bacterial cell wall. Amino acids, nucleosides, heme and cholesterol are then exported by dedicated transporters. Digestion is how phagotrophic protists feed and how animal phagocytes dispose of dead cells and microbes. Loss of a hydrolase or an exporter leaves undigested cargo, and undigested DNA in particular can trigger innate immune signalling.

Boundary: starts with a degradative phagolysosome (the output of MODULE:phagosome_maturation) and ends with digestion products in the cytosol. Phagosome maturation, acidification and lysosome reformation are excluded. Signalling programmes triggered by digestion products are separate modules (MODULE:efferocytosis_induced_macrophage_proliferation, MODULE:efferocytosis_induced_anti_inflammatory_programme, MODULE:heme_induced_iron_recycling_macrophage_differentiation). The tryptophan exporter SLC36A4 is modelled in the anti-inflammatory module. Most of these hydrolases and transporters are general lysosomal machinery. They are included where there is loss-of-function evidence that engulfed cargo is not digested or its products accumulate. LIPA is left out because its efferocytosis evidence is pharmacological and its macrophage knockout is masked by cross-correction from other cells. Taxon scope: digestion of phagocytosed material is eukaryote-wide. DNase II activity is inferred at a eukaryote-level PAINT node. The evidence here comes from mouse, zebrafish, C. elegans, Drosophila and Dictyostelium.