Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection.
BACKGROUND
There are striking similarities between the innate immune systems of invertebrates and vertebrates. Caenorhabditis elegans is increasingly used as a model for the study of innate immunity. Evidence is accumulating that C. elegans mounts distinct responses to different pathogens, but the true extent of this specificity is unclear. Here, we employ direct comparative genomic analyses to explore the nature of the host immune response.


RESULTS
Using whole-genome microarrays representing 20,334 genes, we analyzed the transcriptional response of C. elegans to four bacterial pathogens. Different bacteria provoke pathogen-specific signatures within the host, involving differential regulation of 3.5-5% of all genes. These include genes that encode potential pathogen-recognition and antimicrobial proteins. Additionally, variance analysis revealed a robust signature shared by the pathogens, involving 22 genes associated with proteolysis, cell death and stress responses. The expression of these genes, including those that mediate necrosis, is similarly altered following infection with three bacterial pathogens. We show that necrosis aggravates pathogenesis and accelerates the death of the host.


CONCLUSIONS
Our results suggest that in C. elegans, different infections trigger both specific responses and responses shared by several pathogens, involving immune defense genes. The response shared by pathogens involves necrotic cell death, which has been associated with infection in humans. Our results are the first indication that necrosis is important for disease susceptibility in C. elegans. This opens the way for detailed study of the means by which certain bacteria exploit conserved elements of host cell-death machinery to increase their effective virulence.
Wong
Daniel
D
Centre d'Immunologie de Marseille-Luminy, Université de Méditerranée, Case 906, 13288 Marseille Cedex 9, France.
Bazopoulou
Daphne
D
Pujol
Nathalie
N
Tavernarakis
Nektarios
N
Ewbank
Jonathan J
JJ
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D007107:Immune System; D007109:Immunity; D008954:Models, Biological; D009154:Mutation; D009181:Mycoses / Q000378:metabolism; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins