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The Phagocytic Code Regulating Phagocytosis of Mammalian Cells.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Cockram, Tom OJ 
Dundee, Jacob M 
Popescu, Alma S 
Brown, Guy C 

Abstract

Mammalian phagocytes can phagocytose (i.e. eat) other mammalian cells in the body if they display certain signals, and this phagocytosis plays fundamental roles in development, cell turnover, tissue homeostasis and disease prevention. To phagocytose the correct cells, phagocytes must discriminate which cells to eat using a 'phagocytic code' - a set of over 50 known phagocytic signals determining whether a cell is eaten or not - comprising find-me signals, eat-me signals, don't-eat-me signals and opsonins. Most opsonins require binding to eat-me signals - for example, the opsonins galectin-3, calreticulin and C1q bind asialoglycan eat-me signals on target cells - to induce phagocytosis. Some proteins act as 'self-opsonins', while others are 'negative opsonins' or 'phagocyte suppressants', inhibiting phagocytosis. We review known phagocytic signals here, both established and novel, and how they integrate to regulate phagocytosis of several mammalian targets - including excess cells in development, senescent and aged cells, infected cells, cancer cells, dead or dying cells, cell debris and neuronal synapses. Understanding the phagocytic code, and how it goes wrong, may enable novel therapies for multiple pathologies with too much or too little phagocytosis, such as: infectious disease, cancer, neurodegeneration, psychiatric disease, cardiovascular disease, ageing and auto-immune disease.

Description

Keywords

cancer, cell, immunity, neurodegeneration, opsonin, phagocytosis, signal, signalling, Animals, Calreticulin, Cellular Senescence, Humans, Intercellular Adhesion Molecule-3, Opsonin Proteins, Phagocytosis, Phosphatidylserines, Polysaccharides, Signal Transduction, Synapses

Journal Title

Front Immunol

Conference Name

Journal ISSN

1664-3224
1664-3224

Volume Title

12

Publisher

Frontiers Media SA
Sponsorship
Medical Research Council (MR/L010593/1)
European Commission Horizon 2020 (H2020) Research Infrastructures (RI) (115976)
Biotechnology and Biological Sciences Research Council (1645643)
BBSRC (BB/T508160/1)