Barrier epithelia that are persistently exposed to microbes have evolved potent immune tools to eliminate such pathogens. If mechanisms that control Drosophila systemic responses are well-characterized, the epithelial immune responses remain poorly understood. Here, we performed a genetic dissection of the cascades activated during the immune response of the Drosophila airway epithelium i.e. trachea. We present evidence that bacteria induced-antimicrobial peptide (AMP) production in the trachea is controlled by two signalling cascades. AMP gene transcription is activated by the inducible IMD pathway that acts non-cell autonomously in trachea. This IMD-dependent AMP activation is antagonized by a constitutively active signalling module involving the receptor Toll-8/Tollo, the ligand Spätzle2/DNT1 and Ect-4, the Drosophila ortholog of the human Sterile alpha and HEAT/ARMadillo motif (SARM). Our data show that, in addition to Toll-1 whose function is essential during the systemic immune response, Drosophila relies on another Toll family member to control the immune response in the respiratory epithelium.
Vyšlo v časopise: Toll-8/Tollo Negatively Regulates Antimicrobial Response in the Respiratory Epithelium. PLoS Pathog 7(10): e32767. doi:10.1371/journal.ppat.1002319 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002319
1. MedzhitovR 2007 Recognition of microorganisms and activation of the immune response. Nature 449 819 826
2. FerrandonDImlerJLHetruCHoffmannJA 2007 The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 7 862 874
3. LemaitreBHoffmannJ 2007 The host defense of Drosophila melanogaster. Annu Rev Immunol 25 697 743
4. AkiraSTakedaK 2004 Toll-like receptor signalling. Nat Rev Immunol 4 499 511
5. LemaitreBNicolasEMichautLReichhartJMHoffmannJA 1996 The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86 973 983
6. KumarHKawaiTAkiraS 2009 Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388 621 625
7. RoyetJDziarskiR 2007 Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences. Nat Rev Microbiol 5 264 277
8. MichelTReichhartJMHoffmannJARoyetJ 2001 Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414 756 759
9. LiuCXuZGuptaDDziarskiR 2001 Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J Biol Chem 276 34686 34694
10. BuchonNPoidevinMKwonHMGuillouASottasV 2009 A single modular serine protease integrates signals from pattern-recognition receptors upstream of the Drosophila Toll pathway. Proc Natl Acad Sci U S A 106 12442 12447
11. LeulierFParquetCPili-FlourySRyuJHCaroffM 2003 The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat Immunol 4 478 484
12. WeberANTauszig-DelamasureSHoffmannJALelievreEGascanH 2003 Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat Immunol 4 794 800
13. LemaitreBKromer-MetzgerEMichautLNicolasEMeisterM 1995 A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense. Proc Natl Acad Sci U S A 92 9465 9469
14. ChoeKMLeeHAndersonKV 2005 Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor. Proc Natl Acad Sci U S A 102 1122 1126
15. RametMManfruelliPPearsonAMathey-PrevotBEzekowitzRA 2002 Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416 644 648
16. GottarMGobertVMichelTBelvinMDuykG 2002 The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416 640 644
17. Erturk-HasdemirDBroemerMLeulierFLaneWSPaquetteN 2009 Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proc Natl Acad Sci U S A 106 9779 9784
18. VercelliD 2008 Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 8 169 182
19. BarnesPJ 2008 Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 8 183 192
20. AndrewDJEwaldAJ 2010 Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration. Dev Biol 341 34 55
21. GhabrialALuschnigSMetzsteinMMKrasnowMA 2003 Branching morphogenesis of the Drosophila tracheal system. Annu Rev Cell Dev Biol 19 623 647
22. LubarskyBKrasnowMA 2003 Tube morphogenesis: making and shaping biological tubes. Cell 112 19 28
23. TangHKambrisZLemaitreBHashimotoC 2008 A serpin that regulates immune melanization in the respiratory system of Drosophila. Dev Cell 15 617 626
24. WagnerCIsermannKRoederT 2009 Infection induces a survival program and local remodeling in the airway epithelium of the fly. FASEB J 23 2045 2054
25. RoederTIsermannKKabeschM 2009 Drosophila in asthma research. Am J Respir Crit Care Med 179 979 983
26. TzouPOhresserSFerrandonDCapovillaMReichhartJM 2000 Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 13 737 748
27. FerrandonDJungACCriquiMLemaitreBUttenweiler-JosephS 1998 A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J 17 1217 1227
28. BassetAKhushRSBraunAGardanLBoccardF 2000 The phytopathogenic bacteria Erwinia carotovora infects Drosophila and activates an immune response. Proc Natl Acad Sci U S A 97 3376 3381
29. WagnerCIsermannKFehrenbachHRoederT 2008 Molecular architecture of the fruit fly's airway epithelial immune system. BMC Genomics 9 446
30. LigoxygakisPBuletPReichhartJM 2002 Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila. EMBO Rep 3 666 673
31. SeppoAMataniPSharrowMTiemeyerM 2003 Induction of neuron-specific glycosylation by Tollo/Toll-8, a Drosophila Toll-like receptor expressed in non-neural cells. Development 130 1439 1448
32. AyyarSPistilloDCallejaMBrookfieldAGittinsK 2007 NF-kappaB/Rel-mediated regulation of the neural fate in Drosophila. PLoS One 2 e1178
33. O'NeillLABowieAG 2007 The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7 353 364
34. KambrisZBilakHD'AlessandroRBelvinMImlerJL 2003 DmMyD88 controls dorsoventral patterning of the Drosophila embryo. EMBO Rep 4 64 69
35. Tauszig-DelamasureSBilakHCapovillaMHoffmannJAImlerJL 2002 Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat Immunol 3 91 97
36. YuanSWuKYangMXuLHuangL 2010 Amphioxus SARM involved in neural development may function as a suppressor of TLR signaling. J Immunol 184 6874 6881
37. BelindaLWWeiWXHanhBTLeiLXBowH 2008 SARM: a novel Toll-like receptor adaptor, is functionally conserved from arthropod to human. Mol Immunol 45 1732 1742
38. CouillaultCPujolNReboulJSabatierLGuichouJF 2004 TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol 5 488 494
39. WeberANGangloffMMoncrieffeMCHyvertYImlerJL 2007 Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand. J Biol Chem 282 13522 13531
40. GangloffMMuraliAXiongJArnotCJWeberAN 2008 Structural insight into the mechanism of activation of the Toll receptor by the dimeric ligand Spatzle. J Biol Chem 283 14629 14635
41. TauszigSJouanguyEHoffmannJAImlerJL 2000 Toll-related receptors and the control of antimicrobial peptide expression in Drosophila. Proc Natl Acad Sci U S A 97 10520 10525
42. OoiJYYagiYHuXIpYT 2002 The Drosophila Toll-9 activates a constitutive antimicrobial defense. EMBO Rep 3 82 87
43. Narbonne-ReveauKCharrouxBRoyetJ 2011 Lack of an antibacterial response defect in Drosophila Toll-9 mutant. PLoS One 6 e17470
44. YagiYNishidaYIpYT 2010 Functional analysis of Toll-related genes in Drosophila. Dev Growth Differ 52 771 783
45. ParkerJSMizuguchiKGayNJ 2001 A family of proteins related to Spatzle, the toll receptor ligand, are encoded in the Drosophila genome. Proteins 45 71 80
46. ZhuBPennackJAMcQuiltonPForeroMGMizuguchiK 2008 Drosophila neurotrophins reveal a common mechanism for nervous system formation. PLoS Biol 6 e284
47. SteinD 1995 Pattern formation: The link between ovary and embryo. Curr Biol 5 1360 1363
48. SchneiderDSJinYMorisatoDAndersonKV 1994 A processed form of the Spatzle protein defines dorsal-ventral polarity in the Drosophila embryo. Development 120 1243 1250
49. ChoYSStevensLMSteinD 2010 Pipe-dependent ventral processing of Easter by Snake is the defining step in Drosophila embryo DV axis formation. Curr Biol 20 1133 1137
50. CartyMGoodbodyRSchroderMStackJMoynaghPN 2006 The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol 7 1074 1081
51. KleinoAMyllymakiHKallioJVanha-ahoLMOksanenK 2008 Pirk is a negative regulator of the Drosophila Imd pathway. J Immunol 180 5413 5422
52. AggarwalKRusFVriesema-MagnusonCErturk-HasdemirDPaquetteN 2008 Rudra interrupts receptor signaling complexes to negatively regulate the IMD pathway. PLoS Pathog 4 e1000120
53. LhocineNRibeiroPSBuchonNWepfAWilsonR 2008 PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host Microbe 4 147 158
54. HaEMOhCTBaeYSLeeWJ 2005 A direct role for dual oxidase in Drosophila gut immunity. Science 310 847 850
55. RyuJHNamKBOhCTNamHJKimSH 2004 The homeobox gene Caudal regulates constitutive local expression of antimicrobial peptide genes in Drosophila epithelia. Mol Cell Biol 24 172 185
56. BaasSSharrowMKotuVMiddletonMNguyenK 2010 Sugar-free frosting, a homolog of SAD kinase, drives neural-specific glycan expression in the Drosophila embryo. Development 138 553 563
57. AokiKPerlmanMLimJMCantuRWellsL 2007 Dynamic developmental elaboration of N-linked glycan complexity in the Drosophila melanogaster embryo. J Biol Chem 282 9127 9142
58. CharrouxBRoyetJ 2009 Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the Drosophila immune response. Proc Natl Acad Sci U S A 106 9797 9802
59. KimSChungSYoonJChoiKWYimJ 2006 Ectopic expression of Tollo/Toll-8 antagonizes Dpp signaling and induces cell sorting in the Drosophila wing. Genesis 44 541 549
60. HedengrenMAslingBDushayMSAndoIEkengrenS 1999 Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. Mol Cell 4 827 837
61. RutschmannSKilincAFerrandonD 2002 Cutting edge: the toll pathway is required for resistance to gram-positive bacterial infections in Drosophila. J Immunol 168 1542 1546
62. ParksALCookKRBelvinMDompeNAFawcettR 2004 Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet 36 288 292
63. AbdelsadikARoederT 2010 Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes. BMC Genomics 11 265
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