Immune responses in the epidermis (WP2233)

Caenorhabditis elegans

"Regulation of immune responses in the epidermis by two largely parallel pathways. The p38 MAPK pathway (proteins in this pathway are in black letters) regulates the expression nlp-29, an AMP-encoding gene. A second AMP, encoded by cnc-2, is regulated by neuronally expressed dbl-1 that actives TGFb pathway (blue letters) in the epidermis. The identity of the neurones and whether G-protein signalling is required for neuronal secretion of DBL-1 is not known."


Karen Yook , Susan Coort , and Egon Willighagen


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Caenorhabditis elegans



Pathway Ontology

signaling pathway in the innate immune response


Label Type Compact URI Comment
PIP2 Metabolite chebi:18348
IP3 Metabolite chebi:16595
DAG Metabolite chebi:18035 diacylglycerol
HPLA Metabolite hmdb:HMDB0000755 Through targeted metabolomics analysis we identified the tyrosine derivative 4-hydroxyphenyllactic acid (HPLA) as an endogenous ligand. Our findings reveal DCAR-1 and its cognate ligand HPLA to be triggers of the epidermal innate immune response in C. elegans and highlight the ancient role of GPCRs in host defense.
Type your comment here
DBL-1 GeneProduct wormbase:T25F10.2
NIPI-4 GeneProduct wormbase:F40A3.5 NIPI-4 phenocopies STA-2 and SNF-12
ELT-3 GeneProduct wormbase:K02B9.4
DCAR-1 GeneProduct wormbase:C06H5.7
SMA-3 GeneProduct wormbase:R13F6.9 Neither SMA-2 nor SMA-4 are required in this DBL-1 triggered response
Type your comment here
cnc-2 GeneProduct wormbase:R09B5.3
nlp-29 GeneProduct wormbase:B0213.4
PMK-1 GeneProduct wormbase:B0218.3
SEK-1 GeneProduct wormbase:R03G5.2
NSY-1 GeneProduct wormbase:F59A6.1
PKC-3 GeneProduct wormbase:F09E5.1
TIR-1B GeneProduct wormbase:F13B10.1
TPA-1(PKC delta) GeneProduct wormbase:B0545.1
PLC-3 GeneProduct wormbase:T01E8.3
GPA-12(Galpha) GeneProduct wormbase:F18G5.3
NIPI-3 GeneProduct wormbase:K09A9.1
RACK-1(Gbeta) GeneProduct wormbase:K04D7.1
EGL-8 (PLCbeta) GeneProduct wormbase:B0348.4
STA-2 GeneProduct wormbase:F58E6.1
STA-2 GeneProduct wormbase:F58E6.1
STA-2 GeneProduct wormbase:F58E6.1
STA-2 GeneProduct wormbase:F58E6.1
STA-2 GeneProduct wormbase:F58E6.1
NIPI-4 GeneProduct wormbase:F40A3.5 NIPI-4 phenocopies STA-2 and SNF-12


  1. Signaling in the immune response. Ewbank JJ. WormBook. 2006 Jan 23;1–12. PubMed Europe PMC Scholia
  2. Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-beta signaling pathway in Caenorhabditis elegans epidermis. Zugasti O, Ewbank JJ. Nat Immunol. 2009 Mar;10(3):249–56. PubMed Europe PMC Scholia
  3. Unusual regulation of a STAT protein by an SLC6 family transporter in C. elegans epidermal innate immunity. Dierking K, Polanowska J, Omi S, Engelmann I, Gut M, Lembo F, et al. Cell Host Microbe. 2011 May 19;9(5):425–35. PubMed Europe PMC Scholia
  4. Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans. Zugasti O, Bose N, Squiban B, Belougne J, Kurz CL, Schroeder FC, et al. Nat Immunol. 2014 Sep;15(9):833–8. PubMed Europe PMC Scholia