Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-beta signaling pathway in Caenorhabditis elegans epidermis

Nat Immunol. 2009 Mar;10(3):249-56. doi: 10.1038/ni.1700. Epub 2009 Feb 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antimicrobial Cationic Peptides / immunology
  • Antimicrobial Cationic Peptides / metabolism
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / microbiology
  • Caenorhabditis elegans Proteins / immunology*
  • Caenorhabditis elegans Proteins / metabolism
  • Epidermis / immunology*
  • Epidermis / metabolism
  • Gene Expression Regulation
  • Hypocreales / pathogenicity
  • Multigene Family
  • Neuroimmunomodulation*
  • Neuropeptides / immunology*
  • Neuropeptides / metabolism
  • RNA, Helminth / metabolism
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antimicrobial Cationic Peptides
  • Caenorhabditis elegans Proteins
  • Dbl-1 protein, C elegans
  • Neuropeptides
  • RNA, Helminth
  • Transforming Growth Factor beta
  • p38 Mitogen-Activated Protein Kinases