Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response

Abstract

In response to infection, Caenorhabditis elegans produces an array of antimicrobial proteins. To understand the C. elegans immune response, we have investigated the regulation of a large, representative sample of candidate antimicrobial genes. We found that all these putative antimicrobial genes are expressed in tissues exposed to the environment, a position from which they can ward off infection. Using RNA interference to inhibit the function of immune signaling pathways in C. elegans, we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes. We also show that different bacterial pathogens regulate distinct but overlapping sets of antimicrobial genes. The patterns of genes induced by pathogens do not coincide with any single immune signaling pathway. Thus, even in this simple model system for innate immunity, striking specificity and complexity exist in the immune response. The unique patterns of antimicrobial gene expression observed when C. elegans is exposed to different pathogens or when different immune signaling pathways are perturbed suggest that a large set of yet to be identified pathogen recognition receptors (PRRs) exist in the nematode. These PRRs must interact in a complicated fashion to induce a unique set of antimicrobial genes. We also propose the existence of an “antimicrobial fingerprint,” which will aid in assigning newly identified C. elegans innate immunity genes to known immune signaling pathways.

SUPPLEMENTAL MATERIAL

This research was supported in part by the intramural research program of the NIH, National Institute of Environmental Health Sciences, National Heart, Lung, and Blood Institute, and the National Toxicology Program.

Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources.

We thank Joy Alcedo, Cynthia Kenyon, Adam Driks, Emily Troemel, Fred Ausubel, and the NARSA repository for nematode and bacterial strains. Thanks to Julie Rice, Dan Snyder, and Windy Boyd for assistance with the COPAS Biosort, Brooke Baker for assistance with the confocal microscope, Dave Sherwood for use of his microscope, and Javier Apfeld for critical reading of the manuscript.