Entry
Name
Toll and Imd signaling pathway
Description
Insects, such as Drosophila, have evolved complex mechanisms to combat microbial infection. TOLL and IMD pathways are responsible for the immune response that functions through the production of antimicrobial peptides (AMPs). The TOLL pathway mainly detects fungi, Gram-positive bacteria and virulence factors (proteases et al.). Activation of the TOLL pathway results in degradation of Cactus and localization of Dorsal and Dif to the nucleus. On the other hand, the IMD pathway responses to Gram-negative bacteria and leads to the activation of Relish. Dorsal, Dif and Relish induce the transcriptional up-regulation of AMPs in the nucleus.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
ko04624 Toll and Imd signaling pathway
Orthology
K01446 PGRP; peptidoglycan recognition protein
K02373 FADD; FAS-associated death domain protein
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K03362 FBXW1_11, BTRC, beta-TRCP; F-box and WD-40 domain protein 1/11
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04428 MAP3K4, MEKK4; mitogen-activated protein kinase kinase kinase 4 [EC:2.7.11.25 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 JUN; transcription factor AP-1
K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2
K04729 MYD88; myeloid differentiation primary response protein MyD88
K04730 IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1 ]
K04733 IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K06689 UBE2D, UBC4, UBC5; ubiquitin-conjugating enzyme E2 D [EC:2.3.2.23 ]
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K09031 FOSLN; fos-like antigen, invertebrate
K09254 REL; c-Rel proto-oncogene protein
K10580 UBE2N, BLU, UBC13; ubiquitin-conjugating enzyme E2 N [EC:2.3.2.23 ]
K10704 UBE2V; ubiquitin-conjugating enzyme E2 variant
K16060 BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K20671 PSH; serine protease persephone [EC:3.4.21.-]
K20672 SPE; spatzle-processing enzyme [EC:3.4.21.-]
K20673 GRASS; gram-positive specific serine protease [EC:3.4.21.-]
K20674 MODSP; modular serine protease [EC:3.4.21.-]
K20675 SPIRIT; serine protease immune response integrator
K20676 SPHEROIDE; spheroide [EC:3.4.21.-]
K20692 GNBP3; gram-negative bacteria-binding protein 3
K20693 SPHINX; sphinx [EC:3.4.21.-]
K20695 IM1_2_3; immune-induced peptide 1/2/3
K20697 GNBP1; gram-negative bacteria-binding protein 1
K20700 KEY; NF-kappa-B essential modulator
K20701 PIRK; poor Imd response upon knock-in
K20702 IM4; immune-induced peptide 4
K20703 FAF1; FAS-associated factor 1
K24074 PGRP-LE; peptidoglycan recognition protein LE
K24075 PGRP-LC; peptidoglycan recognition protein LC
K24076 PGRP-LB; peptidoglycan-recognition protein LB
K24077 PGRP-LF; peptidoglycan-recognition protein LF
K24092 PGRP-LA; peptidoglycan recognition protein LA
K24093 PGRP-LD; peptidoglycan recognition protein LD
K24096 PGRP-SB; peptidoglycan recognition protein SB
K24097 PGRP-SD; peptidoglycan recognition protein SD
Compound
Reference
Authors
Merkling SH, van Rij RP
Title
Beyond RNAi: antiviral defense strategies in Drosophila and mosquito.
Journal
Reference
Authors
Valanne S, Wang JH, Ramet M
Title
The Drosophila Toll signaling pathway.
Journal
Reference
Authors
Silverman N, Paquette N, Aggarwal K
Title
Specificity and signaling in the Drosophila immune response.
Journal
Invertebrate Surviv J 6:163-174 (2009)
Reference
Authors
Royet J, Gupta D, Dziarski R
Title
Peptidoglycan recognition proteins: modulators of the microbiome and inflammation.
Journal
Reference
Authors
Buchon N, Silverman N, Cherry S
Title
Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology.
Journal
Reference
Authors
Ferrandon D, Imler JL, Hetru C, Hoffmann JA
Title
The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections.
Journal
Reference
Authors
Stokes BA, Yadav S, Shokal U, Smith LC, Eleftherianos I
Title
Bacterial and fungal pattern recognition receptors in homologous innate signaling pathways of insects and mammals.
Journal
Reference
Authors
Igboin CO, Griffen AL, Leys EJ
Title
The Drosophila melanogaster host model.
Journal
Reference
Authors
Buchon N, Broderick NA, Lemaitre B
Title
Gut homeostasis in a microbial world: insights from Drosophila melanogaster.
Journal
Reference
Authors
Handu M, Kaduskar B, Ravindranathan R, Soory A, Giri R, Elango VB, Gowda H, Ratnaparkhi GS
Title
SUMO-Enriched Proteome for Drosophila Innate Immune Response.
Journal
Reference
Authors
Lindsay SA, Wasserman SA
Title
Conventional and non-conventional Drosophila Toll signaling.
Journal
Reference
Authors
Meinander A, Runchel C, Tenev T, Chen L, Kim CH, Ribeiro PS, Broemer M, Leulier F, Zvelebil M, Silverman N, Meier P
Title
Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling.
Journal
Reference
Authors
Myllymaki H, Valanne S, Ramet M
Title
The Drosophila imd signaling pathway.
Journal
Reference
Authors
Valanne S, Kleino A, Myllymaki H, Vuoristo J, Ramet M
Title
Iap2 is required for a sustained response in the Drosophila Imd pathway.
Journal
Reference
Authors
Levy F, Rabel D, Charlet M, Bulet P, Hoffmann JA, Ehret-Sabatier L
Title
Peptidomic and proteomic analyses of the systemic immune response of Drosophila.
Journal
Reference
Authors
Iatsenko I, Kondo S, Mengin-Lecreulx D, Lemaitre B
Title
PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway.
Journal
Reference
Authors
Zaidman-Remy A, Poidevin M, Herve M, Welchman DP, Paredes JC, Fahlander C, Steiner H, Mengin-Lecreulx D, Lemaitre B
Title
Drosophila immunity: analysis of PGRP-SB1 expression, enzymatic activity and function.
Journal
Reference
Authors
Charroux B, Capo F, Kurz CL, Peslier S, Chaduli D, Viallat-Lieutaud A, Royet J
Title
Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota.
Journal
Reference
Authors
Koyama H, Kato D, Minakuchi C, Tanaka T, Yokoi K, Miura K
Title
Peptidoglycan recognition protein genes and their roles in the innate immune pathways of the red flour beetle, Tribolium castaneum.
Journal
Related pathway
ko04013 MAPK signaling pathway - fly
ko04120 Ubiquitin mediated proteolysis