KEGG   PATHWAY: dme04624
Entry
dme04624                    Pathway                                
Name
Toll and Imd signaling pathway - Drosophila melanogaster (fruit fly)
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
dme04624  Toll and Imd signaling pathway
dme04624

Organism
Drosophila melanogaster (fruit fly) [GN:dme]
Gene
Dmel_CG5008  GNBP3; Gram-negative bacteria binding protein 3 [KO:K20692]
Dmel_CG6895  GNBP1; Gram-negative bacteria binding protein 1 [KO:K20697]
Dmel_CG11709  PGRP-SA; peptidoglycan recognition protein SA, isoform B [KO:K01446]
Dmel_CG8577  PGRP-SC1b; peptidoglycan recognition protein SC1b, isoform B [KO:K01446]
Dmel_CG14745  PGRP-SC2; peptidoglycan recognition protein SC2 [KO:K01446]
Dmel_CG14746  PGRP-SC1a; peptidoglycan recognition protein SC1a [KO:K01446]
Dmel_CG31217  modSP; modular serine protease [KO:K20674] [EC:3.4.21.-]
Dmel_CG5896  grass; Gram-positive specific serine protease, isoform B [KO:K20673] [EC:3.4.21.-]
Dmel_CG32382  sphinx2; sphinx2, isoform C [KO:K20693] [EC:3.4.21.-]
Dmel_CG32383  sphinx1 [KO:K20693] [EC:3.4.21.-]
Dmel_CG2056  spirit; serine protease immune response integrator, isoform C [KO:K20675]
Dmel_CG9675  sphe; spheroide [KO:K20676] [EC:3.4.21.-]
Dmel_CG6367  psh; persephone [KO:K20671] [EC:3.4.21.-]
Dmel_CG1857  nec; necrotic [KO:K20698]
Dmel_CG16705  SPE; Spatzle-Processing enzyme [KO:K20672] [EC:3.4.21.-]
Dmel_CG6134  spz; spatzle, isoform A [KO:K20694]
Dmel_CG9972  spz5; spatzle 5 [KO:K20694]
Dmel_CG5490  Tl; toll, isoform B [KO:K18809]
Dmel_CG7121  Tehao; tehao, isoform B [KO:K18809]
Dmel_CG7250  Toll-6; Toll-6, isoform B [KO:K18809]
Dmel_CG6890  Tollo; tollo [KO:K18809]
Dmel_CG18241  Toll-4; Toll-4 [KO:K18809]
Dmel_CG8595  Toll-7; Toll-7 [KO:K18809]
Dmel_CG8896  18w; 18 wheeler [KO:K18809]
Dmel_CG2078  Myd88; Myd88, isoform B [KO:K04729]
Dmel_CG10520  tub; tube [KO:K04733] [EC:2.7.11.1]
Dmel_CG5974  pll; pelle, isoform B [KO:K04730] [EC:2.7.11.1]
Dmel_CG5848  cact; cactus, isoform E [KO:K04734]
Dmel_CG6794  Dif; Dorsal-related immunity factor, isoform D [KO:K09254]
Dmel_CG6667  dl; dorsal, isoform F [KO:K09254]
Dmel_CG3412  slmb; supernumerary limbs, isoform C [KO:K03362]
Dmel_CG1385  Def; defensin [KO:K20668]
Dmel_CG18106  BomS2; bomanin short 2 [KO:K20695]
Dmel_CG16844  BomS3; bomanin short 3, isoform B [KO:K20695]
Dmel_CG18108  BomS1; bomanin short 1 [KO:K20695]
Dmel_CG15231  Dso1; Daisho1, isoform B [KO:K20702]
Dmel_CG10810  Drs; drosomycin [KO:K20670]
Dmel_CG32282  Drsl4; Drosomycin-like 4 [KO:K20670]
Dmel_CG10812  Drsl5; Drosomycin-like 5 [KO:K20670]
Dmel_CG32279  Drsl2; Drosomycin-like 2 [KO:K20670]
Dmel_CG32274  Drsl1; Drosomycin-like 1 [KO:K20670]
Dmel_CG32268  Drsl6; Drosomycin-like 6 [KO:K20670]
Dmel_CG32283  Drsl3; Drosomycin-like 3 [KO:K20670]
Dmel_CG1373  CecC; cecropin C [KO:K20696]
Dmel_CG1878  CecB; cecropin B [KO:K20696]
Dmel_CG1365  CecA1; cecropin A1 [KO:K20696]
Dmel_CG1367  CecA2; cecropin A2 [KO:K20696]
Dmel_CG7496  PGRP-SD; peptidoglycan recognition protein SD [KO:K24097]
Dmel_CG14704  PGRP-LB; peptidoglycan recognition protein LB, isoform C [KO:K24076] [EC:3.5.1.28]
Dmel_CG9681  PGRP-SB1; peptidoglycan recognition protein SB1 [KO:K24096] [EC:3.5.1.28]
Dmel_CG9697  PGRP-SB2; peptidoglycan recognition protein SB2, isoform A [KO:K24096] [EC:3.5.1.28]
Dmel_CG32042  PGRP-LA; peptidoglycan recognition protein LA, isoform E [KO:K24092]
Dmel_CG33717  PGRP-LD; peptidoglycan recognition protein LD, isoform C [KO:K24093]
Dmel_CG8995  PGRP-LE; peptidoglycan recognition protein LE, isoform B [KO:K24074]
Dmel_CG4432  PGRP-LC; peptidoglycan recognition protein LC, isoform H [KO:K24075]
Dmel_CG4437  PGRP-LF; peptidoglycan recognition protein LF [KO:K24077]
Dmel_CG15678  pirk; poor Imd response upon knock-in, isoform B [KO:K20701]
Dmel_CG7425  eff; effete, isoform B [KO:K06689] [EC:2.3.2.23]
Dmel_CG10862  CG10862; uncharacterized protein [KO:K06689] [EC:2.3.2.23]
Dmel_CG8293  Diap2; Death-associated inhibitor of apoptosis 2, isoform A [KO:K16060]
Dmel_CG10640  Uev1A; Ubiquitin-conjugating enzyme variant 1A, isoform C [KO:K10704]
Dmel_CG18319  ben; bendless, isoform B [KO:K10580] [EC:2.3.2.23]
Dmel_CG3473  CG3473; uncharacterized protein, isoform B [KO:K10580] [EC:2.3.2.23]
Dmel_CG5576  imd; immune deficiency, isoform B [KO:K20699]
Dmel_CG12297  Fadd; Fas-associated death domain [KO:K02373]
Dmel_CG7486  Dredd; death related ced-3/Nedd2-like caspase, isoform E [KO:K04398] [EC:3.4.22.61]
Dmel_CG18492  Tak1; TGF-beta activated kinase 1, isoform A [KO:K04427] [EC:2.7.11.25]
Dmel_CG4803  Takl2; Tak1-like 2 [KO:K04427] [EC:2.7.11.25]
Dmel_CG31421  Takl1; Tak1-like 1 [KO:K04427] [EC:2.7.11.25]
Dmel_CG7417  Tab2; TAK1-associated binding protein 2, isoform B [KO:K04404]
Dmel_CG7717  Mekk1; Mekk1, isoform D [KO:K04428] [EC:2.7.11.25]
Dmel_CG12244  lic; licorne [KO:K04432] [EC:2.7.12.2]
Dmel_CG7393  p38b; p38b MAP kinase [KO:K04441] [EC:2.7.11.24]
Dmel_CG5475  p38a; p38a MAP kinase, isoform C [KO:K04441] [EC:2.7.11.24]
Dmel_CG33338  p38c; p38c MAP kinase [KO:K04441] [EC:2.7.11.24]
Dmel_CG44246  Atf-2; activating transcription factor-2 [KO:K04450]
Dmel_CG3131  Duox; dual oxidase, isoform C [KO:K13411] [EC:1.6.3.1 1.11.1.-]
Dmel_CG4353  hep; hemipterous, isoform A [KO:K04431] [EC:2.7.12.2]
Dmel_CG5680  bsk; basket, isoform F [KO:K04440] [EC:2.7.11.24]
Dmel_CG2275  Jra; Jun-related antigen, isoform A [KO:K04448]
Dmel_CG33956  kay; kayak, isoform F [KO:K09031]
Dmel_CG16910  key; kenny, isoform A [KO:K20700]
Dmel_CG4201  IKKbeta; I-kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
Dmel_CG42734  Ank2; ankyrin 2, isoform N [KO:K09255]
Dmel_CG1651  Ank; ankyrin, isoform E [KO:K09255]
Dmel_CG11992  Rel; relish, isoform A [KO:K02580]
Dmel_CG8400  casp; caspar, isoform C [KO:K20703]
Dmel_CG12763  DptA; diptericin A [KO:K20669]
Dmel_CG10794  DptB; diptericin B [KO:K20669]
Compound
C00027  Hydrogen peroxide
Reference
PMID:22824741
  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
PMID:21209287
  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
PMID:21625362
  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
PMID:22076558
  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
PMID:25421701
  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
PMID:17948019
  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
PMID:25674081
  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
PMID:22368770
  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
PMID:23893105
  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
PMID:26290570
  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
PMID:23632253
  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
PMID:22549468
  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
PMID:24706930
  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
PMID:17343912
  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
PMID:15556270
  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
PMID:27851910
  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
PMID:21364998
  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
PMID:29398649
  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
PMID:26385528
  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
dme04013  MAPK signaling pathway - fly
dme04120  Ubiquitin mediated proteolysis
dme04214  Apoptosis - fly
KO pathway
ko04624   
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