Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-beta signaling pathway in Caenorhabditis elegans epidermis.
After being infected by the fungus Drechmeria coniospora, Caenorhabditis elegans produces antimicrobial peptides in its epidermis, some regulated by a signaling cascade involving a p38 mitogen-activated protein kinase. Here we show that infection-induced expression of peptides of the Caenacin family occurred independently of the p38 pathway. The caenacin (cnc) genes enhanced survival after fungal infection, and neuronal expression of the transforming growth factor-beta homolog DBL-1 promoted cnc-2 expression in the epidermis in a dose-dependent paracrine way. Our results lead to a model in which antifungal defenses are coordinately regulated by a cell-autonomous p38 cascade and a distinct cytokine-like transforming growth factor-beta signal from the nervous system, each of which controls distinct sets of antimicrobial peptide-encoding genes in the epidermis.
Zugasti
Olivier
O
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France.
Ewbank
Jonathan J
JJ
D000818:Animals; D030801:Animals, Genetically Modified; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000276:immunology* / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006999:Hypocreales / Q000472:pathogenicity; D005810:Multigene Family; D015213:Neuroimmunomodulation; D009479:Neuropeptides / Q000276:immunology* / Q000378:metabolism; D018510:RNA, Helminth / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; C117509:Dbl-1 protein, C elegans; D009479:Neuropeptides; D018510:RNA, Helminth; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases