Phagocytosis imprints heterogeneity in tissue-resident macrophages

J Exp Med. 2017 May 1;214(5):1281-1296. doi: 10.1084/jem.20161375. Epub 2017 Apr 21.


Tissue-resident macrophages display varying phenotypic and functional properties that are largely specified by their local environment. One of these functions, phagocytosis, mediates the natural disposal of billions of cells, but its mechanisms and consequences within living tissues are poorly defined. Using a parabiosis-based strategy, we identified and isolated macrophages from multiple tissues as they phagocytosed blood-borne cellular material. Phagocytosis was circadianally regulated and mediated by distinct repertoires of receptors, opsonins, and transcription factors in macrophages from each tissue. Although the tissue of residence defined the core signature of macrophages, phagocytosis imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed CD206, displayed blunted expression of Il1b, and supported tissue homeostasis. Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Interleukin-1beta / metabolism
  • Lectins, C-Type / metabolism
  • Macrophages / physiology*
  • Male
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Opsonin Proteins / physiology
  • Phagocytosis / physiology*
  • Receptors, Cell Surface / metabolism
  • Transcription Factors / physiology


  • Interleukin-1beta
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Opsonin Proteins
  • Receptors, Cell Surface
  • Transcription Factors
  • mannose receptor