Immune responses in the epidermis (Caenorhabditis elegans)

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132PAMPsEpidermisDAF-4NIPI-4NonCanonicalDBL-1 TGF-betapathwayELT-3DBL-1PIP2DAGSNF-12p38 MAPKpathwayDCAR-1IP3HPLA144SMA-6SMA-31cnc-2nlp-29PMK-1SEK-1NSY-1PKC-3TIR-1BTPA-1(PKC delta)PLC-3GPA-12(Galpha)NIPI-3RACK-1(Gbeta)EGL-8 (PLCbeta)STA-2STA-2SNF-12STA-2STA-2PSTA-2NIPI-4


"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."

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Ontology Terms



  1. Zugasti O, Ewbank JJ; ''Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-beta signaling pathway in Caenorhabditis elegans epidermis.''; Nat Immunol, 2009 PubMed Europe PMC Scholia
  2. Dierking K, Polanowska J, Omi S, Engelmann I, Gut M, Lembo F, Ewbank JJ, Pujol N; ''Unusual regulation of a STAT protein by an SLC6 family transporter in C. elegans epidermal innate immunity.''; Cell Host Microbe, 2011 PubMed Europe PMC Scholia
  3. Ewbank JJ; ''Signaling in the immune response.''; WormBook, 2006 PubMed Europe PMC Scholia
  4. Zugasti O, Bose N, Squiban B, Belougne J, Kurz CL, Schroeder FC, Pujol N, Ewbank JJ; ''Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans.''; Nat Immunol, 2014 PubMed Europe PMC Scholia


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107081view14:16, 17 September 2019MaintBotChEBI identifier normalization
106024view11:54, 16 August 2019MaintBotHMDB identifier normalization
80645view07:06, 28 June 2015SusanAdded ID to STA-2
80644view07:01, 28 June 2015SusanAdded id for Sta-1
80642view23:45, 27 June 2015Kyookclarification of SNF-12, STA-2 relationships, added comments to NIPI-4, and SMA-3 dotted line based on J. Ewbank guidance. Need to add references.
80452view22:42, 23 June 2015Kyookpmk-1 - sta-2 arrow, sma-3 to snf-12 arrow, sta-2 regulation of nlp-29
80441view23:06, 22 June 2015Kyook'SMA-2' in JEwbank instructions should be "SMA-3'
80440view22:51, 22 June 2015Kyookresponding to JEwbank 6/22/15 e-mail request: There's no evidence for a sta-2-independent pmk-1-dependent control of nlp-29, so the direct pmk-1-nlp-29 could be removed.

There should a link from SMA-2, via SNF-12/STA-2/NIPI-4, to cnc-2

In the context of
80248view07:27, 28 May 2015Kyook
80235view23:04, 27 May 2015Kyook
80232view22:48, 27 May 2015Kyookchanged primary reference to Ewbank, 2006, WormBook
80231view22:45, 27 May 2015Kyook
80229view20:54, 27 May 2015KyookSNF-12 works with NIPI-4 downstream of PMK-1
80228view00:02, 27 May 2015Kyookconnected WP pathways
80226view21:57, 26 May 2015Kyookadded Dierking et al., 2011
80196view18:07, 20 May 2015Kyookadded HPLA and DCAR-1
80181view18:43, 18 May 2015Kyookupdate for WBook Chapter- removed inferred neuronal input
68464view20:25, 5 July 2013MaintBotUpdated to 2013 gpml schema
53143view02:08, 30 October 2012MaintBotModified categories
49172view00:35, 7 July 2012KyookOntology Term : 'signaling pathway in the innate immune response' added !
49171view00:34, 7 July 2012KyookSpecify description
49170view00:32, 7 July 2012KyookPeriodical save, work in progress
49168view00:21, 7 July 2012KyookNew pathway

External references


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NameTypeDatabase referenceComment
DAF-4ComplexC05D2.1 (WormBase)
DAGMetaboliteCHEBI:18035 (ChEBI) diacylglycerol
DBL-1GeneProductT25F10.2 (WormBase)
DCAR-1GeneProductC06H5.7 (WormBase)
EGL-8 (PLCbeta)GeneProductB0348.4 (WormBase)
ELT-3GeneProductK02B9.4 (WormBase)
GPA-12(Galpha)GeneProductF18G5.3 (WormBase)
HPLAMetaboliteHMDB0000755 (HMDB)
  • 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
IP3MetaboliteCHEBI:16595 (ChEBI)
NIPI-3GeneProductK09A9.1 (WormBase)
NIPI-4GeneProductF40A3.5 (WormBase) NIPI-4 phenocopies STA-2 and SNF-12
NSY-1GeneProductF59A6.1 (WormBase)

DBL-1 TGF-beta

PathwayWP2926 (WikiPathways)
PIP2MetaboliteCHEBI:18348 (ChEBI)
PKC-3GeneProductF09E5.1 (WormBase)
PLC-3GeneProductT01E8.3 (WormBase)
PMK-1GeneProductB0218.3 (WormBase)
RACK-1(Gbeta)GeneProductK04D7.1 (WormBase)
SEK-1GeneProductR03G5.2 (WormBase)
SMA-3GeneProductR13F6.9 (WormBase)
  • Neither SMA-2 nor SMA-4 are required in this DBL-1 triggered response
  • Type your comment here
SMA-6ComplexC32D5.2 (WormBase)
STA-2GeneProductF58E6.1 (WormBase)
TIR-1BGeneProductF13B10.1 (WormBase)
TPA-1(PKC delta)GeneProductB0545.1 (WormBase)
cnc-2GeneProductR09B5.3 (WormBase)
nlp-29GeneProductB0213.4 (WormBase)
p38 MAPK pathwayPathwayWP2925 (WikiPathways)

Annotated Interactions

No annotated interactions

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