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Caenorhabditis elegans: an emerging genetic model for the study of innate immunity

Nature Reviews Genetics volume 4, pages 380–390 (2003)Cite this article

Key Points

  • Interest in innate immunity, the first line of defence of multicellular organisms against infection, has been reawakened in recent years. The mechanisms that are involved are evolutionarily ancient, as shown by the remarkable conservation of the Toll signalling pathway between the model insect Drosophila melanogaster and mammals.

  • The nematode Caenorhabditis elegans has proved its worth as a model organism in fields such as apoptosis and nervous-system development, partly because it possesses many advantages for genetic studies (for example, rapid life cycle, self-fertilization, a large number of progeny and a large mutant collection).

  • This microscopic worm normally lives in the soil where it is in permanent competition with potentially pathogenic bacteria and fungi. But, even after its genome was sequenced, comparisons with Drosophila and other animals raised the question of whether it possesses inducible defence mechanisms against microorganisms.

  • Recently, two signalling pathways that are necessary for the resistance of worms to bacterial infection were identified — the MAPK and TGF-β pathways. Using these signalling cascades, the nematode can integrate infection-associated inputs and respond with specific effectors that contribute to better resistance. However, these pathways are also used in other contexts — for example, during development, which indicates a complex regulation of the relevant signalling cascades.

  • Despite the fact that the similarities with the known components of insect or mammalian immunity are weak, the general defence strategy (recognition, signalling, response) is conserved. So the nematode has the potential to teach us much about the evolutionary origins of immunity, and might reveal as yet uncharacterized aspects of mammalian defences against infection.

  • Importantly, a two-sided approach can be taken with C. elegans, as it can be used to investigate the virulence mechanisms of pathogens. So, with worms, the equilibrium between host and pathogen can be readily addressed.

Abstract

Invaluable insights into how animals, humans included, defend themselves against infection have been provided by more than a decade of genetic studies that have used fruitflies. In the past few years, attention has also turned to another simple animal model, the nematode worm Caenorhabditis elegans. What exactly have we learned from the work in Drosophila? And will research with C. elegans teach us anything new about our response to pathogen attack?

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Figure 1: The Toll and Imd pathways.
Figure 2: Mitogen-activated protein kinase (MAPK) signalling pathways in Caenorabditis elegans are involved in multiple processes.
Figure 3: TGF-β ligands and signalling pathways in Caenorhabditis elegans.

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Acknowledgements

We thank F. M. Ausubel, A. Brunet, A. Coulson, D. Ferrandon, D. Garsin, J. Hodgkin, J.-L. Imler, K. Matsumoto, R. Padgett, J. Royet, G. Silverman and M.-W. Tan for discussions and/or the communication of results before publication. Work in the laboratory of the authors is supported by the Université de la Méditerranée, the Centre National pour la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM) and the French Ministry of Research.

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Authors and Affiliations

  1. Centre d'Immunologie de Marseille Luminy, INSERM/CNRS/Université de la Méditerranée, Case 906, Marseille, 13288 Cedex 9, France

    C. Léopold Kurz & Jonathan J. Ewbank

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  1. C. Léopold Kurz
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  2. Jonathan J. Ewbank
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Correspondence to Jonathan J. Ewbank.

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Databases

Entrez

DAF-2

DAF-16

Imd

Relish

TIG-2

Toll

TLR4

TLR5

TOL-1

UNC-129

UNC-130

FlyBase

Tak1

hep

imd

Mkk4

Toll

Spaetzle

LocusLink

Tlr4

WormBase

daf-2

daf-7

daf-16

pmk-1

pmk-2

nsy-1

sek-1

tig-2

tol-1

unc-43

Further information

Caenorhabditis Genetics Center

Jonathan J. Ewbank's laboratory

Marseille-Génopole post-genomics centre

Michael R. Koelle's laboratory

Protein Families Database of Alignments and HMMs

WormBase

Glossary

MACROPHAGE

A specialized type of white blood cell that can engulf foreign particles and microorganisms.

GRAM NEGATIVE

Bacteria that cannot be coloured with Gram's stain and generally have an lipopolysaccharide-containing outer membrane.

MELANIZATION

A reaction of invertebrates to infection that leads to the production of antimicrobial phenol derivatives and that can involve the encapsulation of a potential pathogen in a melanin envelope.

RNA INTERFERENCE

(RNAi). The specific inactivation of gene expression by a double-stranded RNA molecule.

DAUER

An alternative larval stage that is able to survive adverse conditions.

SIGNALOSOME

A protein complex that is involved in signal transduction.

AUXINS

Plant hormones that control growth.

DORSAL CLOSURE

The concerted movement of epidermal cells that encloses the embryo during early development.

HAEMOCYTES

Specialized blood cells that are important for defence.

AMPHID SENSORY NEURON

A specialized anterior chemosensory neuron.

HYPODERMIS

The external epidermal cell layer.

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Kurz, C., Ewbank, J. Caenorhabditis elegans: an emerging genetic model for the study of innate immunity. Nat Rev Genet 4, 380–390 (2003). https://doi.org/10.1038/nrg1067

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