Evades Immune Recognition of Flagellin in Both Mammals and Plants

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The building blocks of bacterial flagella, flagellin monomers, are potent stimulators of host innate immune systems. Recognition of flagellin monomers occurs by flagellin-specific pattern-recognition receptors, such as Toll-like receptor 5 (TLR5) in mammals and flagellin-sensitive 2 (FLS2) in plants. Activation of these immune systems via flagellin leads eventually to elimination of the bacterium from the host. In order to prevent immune activation and thus favor survival in the host, bacteria secrete many proteins that hamper such recognition. In our search for Toll like receptor (TLR) antagonists, we screened bacterial supernatants and identified alkaline protease (AprA) of Pseudomonas aeruginosa as a TLR5 signaling inhibitor as evidenced by a marked reduction in IL-8 production and NF-κB activation. AprA effectively degrades the TLR5 ligand monomeric flagellin, while polymeric flagellin (involved in bacterial motility) and TLR5 itself resist degradation. The natural occurring alkaline protease inhibitor AprI of P. aeruginosa blocked flagellin degradation by AprA. P. aeruginosa aprA mutants induced an over 100-fold enhanced activation of TLR5 signaling, because they fail to degrade excess monomeric flagellin in their environment. Interestingly, AprA also prevents flagellin-mediated immune responses (such as growth inhibition and callose deposition) in Arabidopsis thaliana plants. This was due to decreased activation of the receptor FLS2 and clearly demonstrated by delayed stomatal closure with live bacteria in plants. Thus, by degrading the ligand for TLR5 and FLS2, P. aeruginosa escapes recognition by the innate immune systems of both mammals and plants.

Vyšlo v časopise: Evades Immune Recognition of Flagellin in Both Mammals and Plants. PLoS Pathog 7(8): e32767. doi:10.1371/journal.ppat.1002206
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002206

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1. AkiraSUematsuSTakeuchiO 2006 Pathogen recognition and innate immunity. Cell 124 783 801

2. HayashiFSmithKDOzinskyAHawnTRYiEC 2001 The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410 1099 1103

3. ChevanceFFHughesKT 2008 Coordinating assembly of a bacterial macromolecular machine. Nat Rev Microbiol 6 455 465

4. SmithKDAndersen-NissenEHayashiFStrobeKBergmanMA 2003 Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol 4 1247 1253

5. Andersen-NissenESmithKDBonneauRStrongRKAderemA 2007 A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. J Exp Med 204 393 403

6. Andersen-NissenESmithKDStrobeKLBarrettSLCooksonBT 2005 Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci U S A 102 9247 9252

7. Gomez-GomezLBollerT 2002 Flagellin perception: a paradigm for innate immunity. Trends Plant Sci 7 251 256

8. RobatzekSChinchillaDBollerT 2006 Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis. Genes Dev 20 537 542

9. ZipfelCRobatzekSNavarroLOakeleyEJJonesJD 2004 Bacterial disease resistance in Arabidopsis through flagellin perception. Nature 428 764 767

10. Gomez-GomezLFelixGBollerT 1999 A single locus determines sensitivity to bacterial flagellin in Arabidopsis thaliana. Plant J 18 277 284

11. LyczakJBCannonCLPierGB 2000 Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2 1051 1060

12. CostertonJWStewartPSGreenbergEP 1999 Bacterial biofilms: a common cause of persistent infections. Science 284 1318 1322

13. SkerrettSJLiggittHDHajjarAMWilsonCB 2004 Cutting edge: myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus. J Immunol 172 3377 3381

14. NouwensASWillcoxMDWalshBJCordwellSJ 2002 Proteomic comparison of membrane and extracellular proteins from invasive (PAO1) and cytotoxic (6206) strains of Pseudomonas aeruginosa. Proteomics 2 1325 1346

15. FeuilletVMedjaneSMondorIDemariaOPagniPP 2006 Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria. Proc Natl Acad Sci U S A 103 12487 12492

16. RamphalRBalloyVJyotJVermaASi-TaharM 2008 Control of Pseudomonas aeruginosa in the lung requires the recognition of either lipopolysaccharide or flagellin. J Immunol 181 586 592

17. BalloyVVermaAKuraviSSi-TaharMChignardM 2007 The role of flagellin versus motility in acute lung disease caused by Pseudomonas aeruginosa. J Infect Dis 196 289 296

18. MatsumotoK 2004 Role of bacterial proteases in pseudomonal and serratial keratitis. Biol Chem 385 1007 1016

19. AzghaniAOKondepudiAYJohnsonAR 1992 Interaction of Pseudomonas aeruginosa with human lung fibroblasts: role of bacterial elastase. Am J Respir Cell Mol Biol 6 652 657

20. ParmelyMGaleAClabaughMHorvatRZhouWW 1990 Proteolytic inactivation of cytokines by Pseudomonas aeruginosa. Infect Immun 58 3009 3014

21. LiehlPBlightMVodovarNBoccardFLemaitreB 2006 Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog 2 e56

22. RooijakkersSHvan KesselKPvan StrijpJA 2005 Staphylococcal innate immune evasion. Trends Microbiol 13 596 601

23. FosterTJ 2005 Immune evasion by staphylococci. Nat Rev Microbiol 3 948 958

24. ChavakisTPreissnerKTHerrmannM 2007 The anti-inflammatory activities of Staphylococcus aureus. Trends Immunol 28 408 418

25. de JongeRvan EsseHPKombrinkAShinyaTDesakiY 2010 Conserved fungal LysM effector Ecp6 prevents chitin-triggered immunity in plants. Science 329 953 955

26. HegeTFeltzerREGrayRDBaumannU 2001 Crystal structure of a complex between Pseudomonas aeruginosa alkaline protease and its cognate inhibitor: inhibition by a zinc-NH2 coordinative bond. J Biol Chem 276 35087 35092

27. StoverCKPhamXQErwinALMizoguchiSDWarrenerP 2000 Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406 959 964

28. FeltzerREGrayRDDeanWLPierceWMJr 2000 Alkaline proteinase inhibitor of Pseudomonas aeruginosa. Interaction of native and N-terminally truncated inhibitor proteins with Pseudomonas metalloproteinases. J Biol Chem 275 21002 21009

29. CaballeroARMoreauJMEngelLSMarquartMEHillJM 2001 Pseudomonas aeruginosa protease IV enzyme assays and comparison to other Pseudomonas proteases. Anal Biochem 290 330 337

30. FelixGDuranJDVolkoSBollerT 1999 Plants have a sensitive perception system for the most conserved domain of bacterial flagellin. Plant J 18 265 276

31. Gomez-GomezLBauerZBollerT 2001 Both the extracellular leucine-rich repeat domain and the kinase activity of FSL2 are required for flagellin binding and signaling in Arabidopsis. Plant Cell 13 1155 1163

32. FanLMZhaoZAssmannSM 2004 Guard cells: a dynamic signaling model. Curr Opin Plant Biol 7 537 546

33. MelottoMUnderwoodWKoczanJNomuraKHeSY 2006 Plant stomata function in innate immunity against bacterial invasion. Cell 126 969 980

34. YonekuraKMaki-YonekuraSNambaK 2003 Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature 424 643 650

35. KollerBKapplerMLatzinPGaggarASchreinerM 2008 TLR expression on neutrophils at the pulmonary site of infection: TLR1/TLR2-mediated up-regulation of TLR5 expression in cystic fibrosis lung disease. J Immunol 181 2753 2763

36. SamakovlisCAslingBBomanHGGateffEHultmarkD 1992 In vitro induction of cecropin genes—an immune response in a Drosophila blood cell line. Biochem Biophys Res Commun 188 1169 1175

37. ZengWHeSY 2010 A prominent role of the flagellin receptor FLAGELLIN-SENSING2 in mediating stomatal response to Pseudomonas syringae pv tomato DC3000 in Arabidopsis. Plant Physiol 153 1188 1198

38. StockerWGramsFBaumannUReinemerPGomis-RuthFX 1995 The metzincins—topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases. Protein Sci 4 823 840

39. GuzzoJDuongFWandersmanCMurgierMLazdunskiA 1991 The secretion genes of Pseudomonas aeruginosa alkaline protease are functionally related to those of Erwinia chrysanthemi proteases and Escherichia coli alpha-haemolysin. Mol Microbiol 5 447 453

40. BestebroerJPoppelierMJUlfmanLHLentingPJDenisCV 2007 Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin-mediated neutrophil rolling. Blood 109 2936 2943

41. de HaasCJVeldkampKEPeschelAWeerkampFVan WamelWJ 2004 Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med 199 687 695

42. HaasDHollowayBW 1976 R factor variants with enhanced sex factor activity in Pseudomonas aeruginosa. Mol Gen Genet 144 243 251

43. NabelGBaltimoreD 1987 An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 326 711 713

44. WalasekPHonekJF 2005 Nonnatural amino acid incorporation into the methionine 214 position of the metzincin Pseudomonas aeruginosa alkaline protease. BMC Biochem 6 21

45. JacobsMAAlwoodAThaipisuttikulISpencerDHaugenE 2003 Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 100 14339 14344

46. PozoMJVan Der EntSVan LoonLCPieterseCM 2008 Transcription factor MYC2 is involved in priming for enhanced defense during rhizobacteria-induced systemic resistance in Arabidopsis thaliana. New Phytol 180 511 523

47. Van der EntSVerhagenBWVan DoornRBakkerDVerlaanMG 2008 MYB72 is required in early signaling steps of rhizobacteria-induced systemic resistance in Arabidopsis. Plant Physiol 146 1293 1304