Distinct innate immune responses to infection and wounding in the C. elegans epidermis.
BACKGROUND
In many animals, the epidermis is in permanent contact with the environment and represents a first line of defense against pathogens and injury. Infection of the nematode Caenorhabditis elegans by the natural fungal pathogen Drechmeria coniospora induces the expression in the epidermis of antimicrobial peptide (AMP) genes such as nlp-29. Here, we tested the hypothesis that injury might also alter AMP gene expression and sought to characterize the mechanisms that regulate the innate immune response.


RESULTS
Injury induces a wound-healing response in C. elegans that includes induction of nlp-29 in the epidermis. We find that a conserved p38-MAP kinase cascade is required in the epidermis for the response to both infection and wounding. Through a forward genetic screen, we isolated mutants that failed to induce nlp-29 expression after D. coniospora infection. We identify a kinase, NIPI-3, related to human Tribbles homolog 1, that is likely to act upstream of the MAPKK SEK-1. We find NIPI-3 is required only for nlp-29 induction after infection and not after wounding.


CONCLUSIONS
Our results show that the C. elegans epidermis actively responds to wounding and infection via distinct pathways that converge on a conserved signaling cassette that controls the expression of the AMP gene nlp-29. A comparison between these results and MAP kinase signaling in yeast gives insights into the possible origin and evolution of innate immunity.
Pujol
Nathalie
N
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France.
Cypowyj
Sophie
S
Ziegler
Katja
K
Millet
Anne
A
Astrain
Aline
A
Goncharov
Alexandr
A
Jin
Yishi
Y
Chisholm
Andrew D
AD
Ewbank
Jonathan J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004817:Epidermis / Q000276:immunology*; D007113:Immunity, Innate / Q000502:physiology*; D007239:Infections / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; D009479:Neuropeptides; D011494:Protein Kinases; C530373:NIPI-3 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases