KEGG   PATHWAY: ko04624
Entry
ko04624                     Pathway                                
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
Pathway map
ko04624  Toll and Imd signaling pathway
ko04624

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
K04398  CASP8; caspase 8 [EC:3.4.22.61]
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]
K04441  P38; p38 MAP 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
K09255  ANK2, ANKB; ankyrin-2
K10580  UBE2N, BLU, UBC13; ubiquitin-conjugating enzyme E2 N [EC:2.3.2.23]
K10704  UBE2V; ubiquitin-conjugating enzyme E2 variant
K13411  DUOX, THOX; dual oxidase [EC:1.6.3.1 1.11.1.-]
K16060  BIRC2_3; baculoviral IAP repeat-containing protein 2/3
K18809  TL; protein toll
K20668  DEF; defensin
K20669  DPT; diptericin
K20670  DRS; drosomycin
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.-]
K20694  SPZ; protein spaetzle
K20695  IM1_2_3; immune-induced peptide 1/2/3
K20696  CEC; cecropin
K20697  GNBP1; gram-negative bacteria-binding protein 1
K20698  NEC; necrotic
K20699  IMD; immune deficiency
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
C00027  Hydrogen peroxide
Reference
  Authors
Merkling SH, van Rij RP
  Title
Beyond RNAi: antiviral defense strategies in Drosophila and mosquito.
  Journal
J Insect Physiol 59:159-70 (2013)
DOI:10.1016/j.jinsphys.2012.07.004
Reference
  Authors
Valanne S, Wang JH, Ramet M
  Title
The Drosophila Toll signaling pathway.
  Journal
J Immunol 186:649-56 (2011)
DOI:10.4049/jimmunol.1002302
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
Nat Rev Immunol 11:837-51 (2011)
DOI:10.1038/nri3089
Reference
  Authors
Buchon N, Silverman N, Cherry S
  Title
Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology.
  Journal
Nat Rev Immunol 14:796-810 (2014)
DOI:10.1038/nri3763
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
Nat Rev Immunol 7:862-74 (2007)
DOI:10.1038/nri2194
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
Front Microbiol 6:19 (2015)
DOI:10.3389/fmicb.2015.00019
Reference
  Authors
Igboin CO, Griffen AL, Leys EJ
  Title
The Drosophila melanogaster host model.
  Journal
J Oral Microbiol 4:JOM-4-10368 (2012)
DOI:10.3402/jom.v4i0.10368
Reference
  Authors
Buchon N, Broderick NA, Lemaitre B
  Title
Gut homeostasis in a microbial world: insights from Drosophila melanogaster.
  Journal
Nat Rev Microbiol 11:615-26 (2013)
DOI:10.1038/nrmicro3074
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
G3 (Bethesda) 5:2137-54 (2015)
DOI:10.1534/g3.115.020958
Reference
  Authors
Lindsay SA, Wasserman SA
  Title
Conventional and non-conventional Drosophila Toll signaling.
  Journal
Dev Comp Immunol 42:16-24 (2014)
DOI:10.1016/j.dci.2013.04.011
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
EMBO J 31:2770-83 (2012)
DOI:10.1038/emboj.2012.121
Reference
  Authors
Myllymaki H, Valanne S, Ramet M
  Title
The Drosophila imd signaling pathway.
  Journal
J Immunol 192:3455-62 (2014)
DOI:10.4049/jimmunol.1303309
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
Dev Comp Immunol 31:991-1001 (2007)
DOI:10.1016/j.dci.2007.01.004
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
Biochimie 86:607-16 (2004)
DOI:10.1016/j.biochi.2004.07.007
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
Immunity 45:1013-1023 (2016)
DOI:10.1016/j.immuni.2016.10.029
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
PLoS One 6:e17231 (2011)
DOI:10.1371/journal.pone.0017231
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
Cell Host Microbe 23:215-228.e4 (2018)
DOI:10.1016/j.chom.2017.12.007
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
J Invertebr Pathol 132:86-100 (2015)
DOI:10.1016/j.jip.2015.09.003
Related
pathway
ko04013  MAPK signaling pathway - fly
ko04120  Ubiquitin mediated proteolysis
ko04214  Apoptosis - fly

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