Drosophila Innate Immunity

Abstract

Drosophila melanogaster is a useful model for studying innate immunity that has been used to identify and characterise the role of the Toll pathway and nuclear factor‐κB (NFκB) signalling in both insects and mammals. When flies encounter a pathogen, two pattern recognition pathways, Toll and imd, induce a humoral immune response consisting primarily of antimicrobial peptide production. Drosophila also has a cellular immune response in which phagocytic cells engulf and destroy foreign invaders; a melanisation response that generates reactive oxygen species; and an antiviral RNAi (ribonucleic acid interference) response. Application of Drosophila model has already taught us much about innate immunity. As we expand our research to take a more comprehensive look at how a host responds to infection and what determines the outcome of that infection we can continue to learn more about this complex system from the simple fruitfly.

Key Concepts:

  • Drosophila can be used as a model system to study the innate immune system.

  • The Drosophila immunity consists of humoral, cellular and melanisation responses.

  • The humoral immune response involves antimicrobial peptide production, which is induced by the recognition of pathogen‐associated molecular patterns (PAMPs) by patter recognition receptors (PRRs).

  • Two NFκB signalling pathways, Toll and imd, regulate the AMP response to fungal, bacterial and viral pathogens.

  • The cellular immune response is enacted by phagocytic cells known as hemocytes.

  • The melanisation response encapsulates foreign invaders with melanin and produces reactive oxygen species to kill microbes.

  • The fly also has barrier epithelia, native intestinal flora and an RNAi antiviral response which contribute to innate immunity.

  • Physiological and environmental factors can affect the outcome of an infection, including sleep and additional immune challenges.

  • The susceptibility of a fruitfly to bacterial infection depends both on its ability to resist a pathogenic infection and prevent bacterial growth and also its ability to tolerate the bacteria and the consequences of its own immune response.

Keywords: Drosophila; innate immunology; Toll; antimicrobial peptides; melanisation

Figure 1.

The Toll and imd pathways regulate the Drosophila inducible antimicrobial peptide response. (A) The toll pathway recognises viral, fungal and bacterial pathogens. Fungi are recognised in a manner that is dependent on the serine protease Persephone (Psh), whrease bacterial lysine‐type peptidoglycan is recognised by peptidoglycan recognition proteins (PGRP‐SA and PGRP‐SD) and Gram‐negative‐binding proteins (GNBP). Both pathways lead to the activation of the Toll ligand, Spaetzle, which then binds to the Toll receptor. This leads to downstream signalling through MyD88, Tube and Pele which leads to the degradation of Cactus, the IκB homologue. This releases the NFκB factors Dif or Dorsal, which translocate to the cell nucleus and initiate transcription of antimicrobial peptide genes. (B) The imd pathway recognised DAP‐type peptidoglycan through the receptors PGRP‐LC and PGRP‐LE. This activates a signal transduction pathway that requires TAK1, Fadd and the caspase DREDD, which leads to the activation of the IKK complex consisting of two subunits, Kenny and Ird5. The activated complex then phosphorylates Relish, an NFκB precursor, which then also translocates to the nucleus and initiates transcription.

Figure 2.

A comprehensive view of the innate immune system of Drosophila. The fly has a number of innate immune mechanisms and responses to protect itself from infection by microbial pathogens. (A) Barrier epithelia serves as physical protection to keep foreign invaders out. (B) In the gut, native intestinal flora are regulated by antimicrobial peptides and a reactive oxygen response. (C) The cellular immune response consisting primarily of phagocytic hemocytes engulfs and destroys invading microbes. (D) The humoral immune response fights microbes with antimicrobial peptides that are secreted by the fat body and are regulated by Toll and imd signalling. (E) The melanisation response sequesters pathogens and damages them with reactive oxygen species.

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Further Reading

Aggarwal K and Silverman N (2008b) Positive and negative regulation of the Drosophila immune response. BMB Report 41(4): 267–277.

Beutler B and Moresco EM (2008) The forward genetic dissection of afferent innate immunity. Current Topics in Microbiology and Immunology 321: 3–26.

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Stuart LM and Ezekowitz RA (2008) Phagocytosis and comparative innate immunity: learning on the fly. Nature Reviews. Immunology 8(2): 131–141.

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Moule, Madeleine G, and Schneider, David S(May 2010) Drosophila Innate Immunity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021845]