Toll, IMD, JAK/STAT pathways for immune response to pathogens (WP3856)

Anopheles gambiae

The presence P. berghei signals proteins Toll Pathway through proteins PGRP-S, CLIPB13, CLIPC8, and SPZ2. Toll activates death domain-containing molecules (MyD88, Tube, Pelle). Pellino ubiquinates Pelle which allows TRAF to activate REL1 by the ubiquitination of cactus. REL1 translocates to nucleus to upregulate immune genes. The IMD pathway is activated by presence of P. faciparum that starts a cascade of activation of Fadd, Dredd, Tak1/Tab2 coomplex and leads to the activation, translocation, and effector gene promotion of Relish. The Effete/Uev1a/Bendless/IAP2 inhibits the CASPL1/Dredd complex. The JAK/STAT pathway is activated by presence of P. vivax and unpaired gene particles binding to dome/JAK/STAT complex leading to the actIvation of the STAT complex which translocates to the nucleus to promote transcription of effector genes. This pathway was taken from Figure 2B of Severo et al.


AAR&Co , Martina Summer-Kutmon , Friederike Ehrhart , Kristina Hanspers , and Eric Weitz


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited By

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.


Anopheles gambiae



Pathway Ontology

immune response pathway


Label Type Compact Identifier Comment
IKK1 GeneProduct ensembl:AGAP009166
PGRPS1 GeneProduct ensembl:AGAP000536
TRAF6 GeneProduct ensembl:AGAP000388 TRAF not specified
IMD GeneProduct ensembl:AGAP004959
CASPL1 GeneProduct ensembl:AGAP011693
REL1 GeneProduct ensembl:AGAP009515 Dorsal Not Specified
IAP2 GeneProduct ensembl:AGAP011326
Relish GeneProduct ncbiprotein:17137094
TUBE GeneProduct ensembl:AGAP003062
STAT2 GeneProduct ensembl:AGAP000099
PELLE GeneProduct ensembl:AGAP002966
SPZ2 GeneProduct ensembl:AGAP006483
CACT GeneProduct ensembl:AGAP007938
DOME GeneProduct ensembl:AGAP010083
PGRPLC GeneProduct ensembl:AGAP005203
CLIPB13 GeneProduct ensembl:AGAP004855
FADD GeneProduct ensembl:AGAP007173
DOME GeneProduct ensembl:AGAP010083
STAT2 GeneProduct ensembl:AGAP000099
STAT GeneProduct ensembl:AGAP000099
STAT GeneProduct ensembl:AGAP000099
STAT GeneProduct ensembl:AGAP000099
STAT GeneProduct ensembl:AGAP000099
REL1 GeneProduct ensembl:AGAP009515 Dorsal Not Specified
PGRPS2 GeneProduct ensembl:AGAP006343
PGRPS3 GeneProduct ensembl:AGAP006342
REL2 GeneProduct ensembl:AGAP006747


  1. The “ubiquitous” reality of vector immunology. Severo MS, Sakhon OS, Choy A, Stephens KD, Pedra JHF. Cell Microbiol. 2013 Jul;15(7):1070–8. PubMed Europe PMC Scholia