id: MODULE:phagocytosis
title: Phagocytosis
description: >-
  Phagocytosis is how eukaryotic cells take in large particles: microbes, dead
  or dying cells, aged red cells and debris. A receptor on the phagocyte
  recognises the particle, Rho-family GTPases drive actin to wrap the membrane
  around it, and the sealed phagosome then matures by fusing with endosomes and
  lysosomes into an acidic, degradative phagolysosome. There the cargo is
  digested and its products are returned to the cytosol. Protists use this
  route to feed; animal phagocytes use it for defence and for clearing cells.
  In animals, the digested cargo can also switch on programmes in the phagocyte
  itself, such as proliferation, priming, differentiation or an
  anti-inflammatory response, that depend on what was eaten.
status: DRAFT
scope: ABSTRACT
references:
  - id: PMID:25319336
    title: "Phagocytosis: receptors, signal integration, and the cytoskeleton."
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: PubMed-verified review (Freeman & Grinstein 2014); abstract cached.
  - id: PMID:22560866
    title: How nascent phagosomes mature to become phagolysosomes.
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: PubMed-verified review (Fairn & Grinstein 2012).
evidence:
  - source_id: PMID:25319336
    title: "Phagocytosis: receptors, signal integration, and the cytoskeleton."
    statement: Phagocytosis serves both defence and tissue homeostasis.
    supporting_text: >-
      Phagocytosis is a remarkably complex and versatile process: it contributes to
      innate immunity through the ingestion and elimination of pathogens, while also
      being central to tissue homeostasis and remodeling by clearing effete cells.
notes: >-
  This is an umbrella module. Each step is a separate module, included by
  reference. The first three steps are the phagocytic pathway itself and are
  shared by eukaryotes. The post-phagocytic programmes are optional and
  lineage-specific: each is triggered by a particular kind of cargo and has
  so far been shown in one animal lineage.

  In GO, GO:0006909 phagocytosis includes phagosome maturation (part_of since
  go-ontology#32152). The post-phagocytic programmes have no GO home; specific
  terms were proposed in go-ontology#32748. See projects/PHAGOCYTOSIS.md.
module:
  id: phagocytosis
  label: Phagocytosis
  module_type: BIOLOGICAL_PROCESS
  concepts:
    - preferred_term: phagocytosis
      term:
        id: GO:0006909
        label: phagocytosis
  context:
    taxa:
      - preferred_term: Eukaryota
        term:
          id: NCBITaxon:2759
          label: Eukaryota
    cell_types:
      - preferred_term: phagocyte
        term:
          id: CL:0000234
          label: phagocyte
  parts:
    - order: 1
      role: recognition and engulfment
      node:
        id: engulfment_step
        label: Phagocytic engulfment
        module_ref: phagocytic_engulfment
    - order: 2
      role: phagosome maturation
      node:
        id: maturation_step
        label: Phagosome maturation
        module_ref: phagosome_maturation
    - order: 3
      role: cargo digestion
      node:
        id: degradation_step
        label: Phagolysosomal cargo degradation
        module_ref: phagolysosomal_cargo_degradation
    - order: 4
      role: post-phagocytic programmes
      optional: true
      node:
        id: post_phagocytic_programmes
        label: Post-phagocytic programmes
        module_type: BIOLOGICAL_PROCESS
        description: >-
          Programmes the phagocyte runs because of what it engulfed. Each is
          triggered by a component of a particular cargo and has its own
          signalling chain and output. None is required for phagocytosis itself.
        variant_sets:
          - id: programme
            label: Programme triggered by cargo
            axis: cargo signal and cellular output
            selection: ONE_OR_MORE
            variants:
              - id: proliferation_programme
                label: Efferocytosis-induced macrophage proliferation
                module_ref: efferocytosis_induced_macrophage_proliferation
              - id: priming_programme
                label: Efferocytosis-induced macrophage priming
                module_ref: efferocytosis_induced_macrophage_priming
              - id: anti_inflammatory_programme
                label: Efferocytosis-induced anti-inflammatory programme
                module_ref: efferocytosis_induced_anti_inflammatory_programme
              - id: heme_differentiation_programme
                label: Heme-induced iron-recycling macrophage differentiation
                module_ref: heme_induced_iron_recycling_macrophage_differentiation
  connections:
    - source: engulfment_step
      target: maturation_step
      connection_type: PRECEDES
      description: Engulfment delivers the sealed nascent phagosome.
    - source: maturation_step
      target: degradation_step
      connection_type: PRECEDES
      description: Maturation delivers the hydrolases and the acidic lumen that digestion needs.
    - source: degradation_step
      target: post_phagocytic_programmes
      connection_type: PROVIDES_INPUT_FOR
      description: >-
        Digestion products (DNA fragments, heme, sterols, fatty acids,
        tryptophan, methionine) are the signals for most programmes. The MERTK
        arm of the proliferation programme and the priming programme are
        triggered before or during engulfment.