Anti-Fungal Innate Immunity in C. elegans Is Enhanced by Evolutionary Diversification of Antimicrobial Peptides

Nathalie Pujol,Daniel Wong,Olivier Zugasti,C Léopold Kurz,Hinrich Schulenburg,Carole Couillault,Jonathan J Ewbank,Frederick M Ausubel

doi:10.1371/journal.ppat.1000105

Abstract

Encounters with pathogens provoke changes in gene transcription that are an integral part of host innate immune responses. In recent years, studies with invertebrate model organisms have given insights into the origin, function, and evolution of innate immunity. Here, we use genome-wide transcriptome analysis to characterize the consequence of natural fungal infection in Caenorhabditis elegans. We identify several families of genes encoding putative antimicrobial peptides (AMPs) and proteins that are transcriptionally up-regulated upon infection. Many are located in small genomic clusters. We focus on the nlp-29 cluster of six AMP genes and show that it enhances pathogen resistance in vivo. The same cluster has a different structure in two other Caenorhabditis species. A phylogenetic analysis indicates that the evolutionary diversification of this cluster, especially in cases of intra-genomic gene duplications, is driven by natural selection. We further show that upon osmotic stress, two genes of the nlp-29 cluster are strongly induced. In contrast to fungus-induced nlp expression, this response is independent of the p38 MAP kinase cascade. At the same time, both involve the epidermal GATA factor ELT-3. Our results suggest that selective pressure from pathogens influences intra-genomic diversification of AMPs and reveal an unexpected complexity in AMP regulation as part of the invertebrate innate immune response.

Highlights

Two strategies exist for organisms that suffer from predation or infection in their natural environment
To characterize the response of C. elegans to a natural fungal infection, we have analyzed changes in gene expression in worms infected with D. coniospora
Transcriptional response of C. elegans to fungal infection In this study, after an unbiased microarray analysis of genes affected by natural fungal infection in the epidermis of C. elegans, we focused on putative antimicrobial peptides (AMPs) genes, as they are the most prominent class of up-regulated genes

Summary

Introduction

Two strategies exist for organisms that suffer from predation or infection in their natural environment. They can invest in constitutive defenses that will offer them permanent protection, and they can use inducible defenses that are activated only when they are in danger [1]. In C. elegans, the epidermis is at the interface with the environment and is expected to play a key role in defense. It is responsible for the production of the collagen-rich cuticle that surrounds the nematode and provides a permanent physical barrier to pathogens. Nematophagous fungi such as Drechmeria coniospora adhere to the cuticle and infect nematodes directly via the epidermis [5]

Methods

Discussion

Conclusion