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  • Review Article
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Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates

Nature Reviews Immunology volume 10, pages 47–58 (2010)Cite this article

Subjects

Key Points

  • The nematode Caenorhabditis elegans was developed as a model for studying bacterial virulence and innate immunity in 1999. C. elegans does not have circulating cells and seems to rely almost exclusively on epithelial immunity to combat pathogen attack. Several parallel immune response pathways have been identified that activate distinct but partially overlapping sets of immune effectors. Despite its simplicity, the C. elegans immune response is highly pathogen specific and different pathogens activate distinct immune response pathways.

  • Although C. elegans has a single Toll-like receptor (TLR), myeloid differentiation primary-response protein 88 (MYD88) and nuclear factor-κB (NF-κB) are not encoded in the C. elegans genome or in the genomes of other nematode species. Moreover, the single C. elegans TLR does not seem to have an important role in the immune response. Because some cnidaria (such as the sea anemone Nematostella vectensis) have TLRs, MYD88 and NF-κB, it seems that TLR signalling has been lost in the nematode lineage.

  • A highly conserved p38 mitogen-activated protein kinase (MAPK) signalling cascade has a central role in the C. elegans immune response as it does in mammals. The p38 MAPK pathway is required for the activation of a set of immune effectors that are required to maintain a basal level of immune function.

  • The p38 MAPK signalling pathway is active during both infection and wounding and functions in at least the intestine, neurons and epidermis in response to pathogen infection.

  • Several highly conserved metazoan signalling pathways have dual roles, functioning as important components of the C. elegans immune response. It is of interest to determine whether the same pathways function in immune signalling throughout metazoan evolution, including acting in concert with TLR pathways in mammals.

  • In addition to its role in stress resistance, lifespan extension and metabolic regulation in C. elegans, the DAF-2–DAF-16 insulin signalling pathway confers resistance to a wide variety of pathogens when DAF-16 is constitutively activated.

  • The C. elegans β-catenin homologue β-catenin/armadillo-related family member 1 (BAR-1) and the downstream homoebox protein egg laying defective protein 5 (EGL-5) have central roles in activating the C. elegans immune response to infection by Staphylococcus aureus but not Pseudomonas aeruginosa. Roles for β-catenin and homeobox proteins in immune signalling in flies and mammals have also been recently shown.

  • The G protein-coupled receptor FSHR-1 is the first candidate immune receptor to be identified in C. elegans.

Abstract

The genetically tractable model organism Caenorhabditis elegans was first used to model bacterial virulence in vivo a decade ago. Since then, great strides have been made in identifying the host response pathways that are involved in its defence against infection. Strikingly, C. elegans seems to detect, and respond to, infection without the involvement of its homologue of Toll-like receptors, in contrast to the well-established role for these proteins in innate immunity in mammals. What, therefore, do we know about host defence mechanisms in C. elegans and what can they tell us about innate immunity in higher organisms?

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Figure 1: The Caenorhabditis elegans intestine.
Figure 2: Mitogen-activated protein kinase signalling is conserved in Caenorhabditis elegans.
Figure 3: Components of Toll-like receptor signalling in bilateria and cnidaria.
Figure 4: Parallel signalling pathways in the induction of Caenorhabditis elegans host defence.

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Acknowledgements

The unpublished observations cited in this review were funded by US National Institutes of Health grants R01 AI64332 and PO1 AI44220 awarded to F.M.A.

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Authors and Affiliations

  1. Department of Pediatrics, Harvard Medical School and Program in Developmental Immunology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Javier E. Irazoqui

  2. Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Jonathan M. Urbach & Frederick M. Ausubel

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  1. Javier E. Irazoqui
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  2. Jonathan M. Urbach
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Correspondence to Frederick M. Ausubel.

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Glossary

Hermaphrodite

An organism that has both male and female reproductive organs.

RNA interference

The silencing of gene expression by the introduction of double-stranded RNA that triggers the specific degradation of a homologous target mRNA, often accompanied by a concomitant decrease in production of the encoded protein.

Microarray

A technique for measuring the transcription of genes. It involves the hybridization of fluorescently labelled cDNA prepared from a cell or tissue of interest to glass slides or other surfaces dotted with oligodeoxynucleotides or cDNA that represents all genes in the species.

Quantitative reverse transcription PCR

(qRT-PCR). A quantitative PCR method that is used to measure relative or absolute mRNA concentrations.

Scaffold protein

A protein that functions as a support to assemble a multiprotein complex.

Coelomate

An animal that has an internal body cavity derived from the mesoderm.

Bilateria

Members of the animal kingdom that have bilateral symmetry — the property of having two similar sides, with definite upper and lower surfaces, and anterior and posterior ends.

Neuropeptide-like peptides

A family of short peptides with sequence homology to YGGW-amide neuropeptides, which can be induced during infection.

Caenacins

A family of peptides related to neuropeptide-like peptides, which can be induced during infection.

Epistasis

An interaction between non-allelic genes, such that one gene masks, interferes with or enhances the expression of the other gene.

Reverse genetic approach

A genetic approach that proceeds from genotype to phenotype by gene manipulation techniques, such as homologous recombination in embryonic stem cells and RNA interference.

Homeobox transcription factors

The genes encoding these factors contain a 180-base pair sequence encoding the homeodomain and are involved in the regulation of animal and plant development. This sequence encodes a DNA-binding helix–turn–helix motif (the homeodomain), indicating that homeodomain-containing gene products function as transcription factors.

Leucine-rich repeat (LRR) domains

Domains that contain LRRs have a conserved solenoid structure, typically 20–29 residues in length and containing an 11 amino acid consensus sequence, LXXLXLXX(N or C)XL, in which X denotes any amino acid. These domains lack considerable identity or similarity in the amino acids surrounding this structure, both between and among families. Sequence substitutions in LRR-containing proteins are associated with changes in specificity and relative affinity towards LRR domain-binding partners.

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Irazoqui, J., Urbach, J. & Ausubel, F. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 10, 47–58 (2010). https://doi.org/10.1038/nri2689

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