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  • Review Article
  • Published:

Phagocytosis and comparative innate immunity: learning on the fly

Nature Reviews Immunology volume 8, pages 131–141 (2008)Cite this article

Key Points

  • Phagocytosis, the internalization of particles by cells, is involved in development, tissue homeostasis and host defence. Aspects of this process are highly conserved between species and hence studies in model organisms, such as Drosophila melanogaster, have been informative.

  • Particle internalization is not simply a mechanism of waste disposal but rather essential for the formation of the phagosome, the organelle that is generated around the internalized particle. As in mammals, D. melanogaster phagosomes are highly complex compartments and are central to many of the effector functions of phagocytes.

  • Phagocytosis is triggered after ligation of cell-surface receptors. Similar to mammals, D. melanogaster uses multiple mechanisms of bacterial recognition, such as complement-like opsonization and scavenger receptors. In addition, studies in D. melanogaster have highlighted a new family of phagocytic receptors that use epidermal growth factor (EGF)-like repeats to bind ligands.

  • Fruit flies have an alternative to the highly variable antibodies found in mammals and instead use DSCAM (Down syndrome cell-adhesion molecule), an immunoglobulin-superfamily member that shows remarkable variability, that may act as both an opsonin and a cell-surface receptor.

  • RNA-interference-based screens have shown that much of the machinery downstream of the cell-surface receptors are common between flies and humans. Studies in D. melanogaster have also suggested roles for the coatamer protein complex and the exocyst complex in the process of phagocytosis.

  • In addition, studies in D. melanogaster have added to our understanding of the role of phagocytosis in pathogen sensing. Furthermore, D. melanogaster phagocytes may potentially be involved in immune adaptation and the processing of internalized antigens.

Abstract

Phagocytosis, the engulfment of material by cells, is a highly conserved process that arose before the development of multicellularity. Phagocytes have a key role in embryogenesis and also guard the portals of potential pathogen entry. They discriminate between diverse particles through the array of receptors expressed on their surface. In higher species, arguably the most sophisticated function of phagocytes is the processing and presentation of antigens derived from internalized material to stimulate lymphocytes and long-lived specific immunity. Central to these processes is the generation of a phagosome, the organelle that forms around internalized material. As we discuss in this Review, over the past two decades important insights into phagocytosis have been gleaned from studies in the model organism Drosophila melanogaster.

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Figure 1: Phagocytosis delivers the bound particle from the cell surface into the phagosome.
Figure 2: The phagosome is a multifunctional organelle.
Figure 3: An emerging superfamily of EGF-like-repeat-containing phagocytic receptors and opsonins.
Figure 4: Insect DSCAM and mammalian immunoglobulins display common functional characteristics.
Figure 5: Nutrient acquisition is possibly the evolutionary origin of the link between phagocytosis and bacterial recognition.

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Acknowledgements

We thank members of the laboratory of Developmental Immunology, Massachusetts General Hospital, for continuous inspiration. Our particular thanks go to C. Kocks for help with the original figure 3 and for critical reading and helpful input into the manuscript. Finally, we apologize to our colleagues whose work we have been unable to cite or discuss owing to space constraints.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Developmental Immunology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02144, Massachusetts, USA

    Lynda M. Stuart

  2. Merck Research Laboratories, Lincoln Avenue, Rahway, 07065, New Jersey, USA

    R. Alan Ezekowitz

Authors
  1. Lynda M. Stuart
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  2. R. Alan Ezekowitz
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Correspondence to Lynda M. Stuart.

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FURTHER INFORMATION

Lynda M. Stuart's homepage

Laboratory of Developmental Immunology

The Interactive Fly

Glossary

Phagocytes

Cells such as macrophages and neutrophils that internalize particulate material in an actin-dependent manner. Derived from the greek phagein (to eat) and kytos (cell).

Apoptotic cell

A cell that has died by a genetically regulated programme of cell death. It is characterized by cell shrinkage, chromatin condensation, cell-membrane blebbing and DNA fragmentation. Eventually, the cell breaks up into many membrane-bound apoptotic bodies, which are phagocytosed by neighbouring cells.

Holometabolous insects

Insects, such as Drosophila melanogaster, that have a pupal stage during which they undergo complete reorganization and metamorphosis.

Haemocytes

Cells found within the haemolymph of an insect that are equivalent to the blood cells in vertebrates.

RNA interference

The silencing of gene expression by the introduction of double-stranded RNAs that trigger the specific degradation of a homologous target mRNA and often subsequently decrease production of the encoded protein.

Opsonin

A soluble molecule that, when bound to a particle, enhances uptake of the particle by phagocytosis.

Pattern-recognition receptors

Receptors that recognize molecular patterns often associated with pathogens, such as lipopolysaccharide found in the bacterial cell walls of Gram-negative microorganisms. They also recognize molecular patterns expressed by non-pathogenic bacteria.

N-ethyl-N-nitrosourea (ENU) mutagenesis

An alkylating agent and potent mutagen that when given to mice efficiently induces random mutations.

Gene rearrangement

The ordered rearrangement of variable regions of genes encoding antigen receptors that contributes to increase receptor diversity.

Somatic hypermutation

The process by which antigen-activated B cells in germinal centres mutate their rearranged immunoglobulin genes. The B cells are subsequently selected for those expressing the 'best' mutations on the basis of the ability of the surface immunoglobulin to bind antigen.

Convergent evolution

The development of similar characteristics in organisms that are unrelated as a consequence of how each adapts to a similar evolutionary pressure but which occurs after evolutionary divergence.

Pseudopod

A transient protrusion from the cell during cell movement or to envelop a particle that is to be internalized.

Exocytosis

The release of material contained within vesicles by fusion of the vesicles with the plasma membrane.

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Stuart, L., Ezekowitz, R. Phagocytosis and comparative innate immunity: learning on the fly. Nat Rev Immunol 8, 131–141 (2008). https://doi.org/10.1038/nri2240

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