Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in

English version České info

Infected animals will produce reactive oxygen species (ROS) and other inflammatory molecules that help fight pathogens, but can inadvertently damage host tissue. Therefore specific responses, which protect and repair against the collateral damage caused by the immune response, are critical for successfully surviving pathogen attack. We previously demonstrated that ROS are generated during infection in the model host Caenorhabditis elegans by the dual oxidase Ce-Duox1/BLI-3. Herein, an important connection between ROS generation by Ce-Duox1/BLI-3 and upregulation of a protective transcriptional response by SKN-1 is established in the context of infection. SKN-1 is an ortholog of the mammalian Nrf transcription factors and has previously been documented to promote survival, following oxidative stress, by upregulating genes involved in the detoxification of ROS and other reactive compounds. Using qRT-PCR, transcriptional reporter fusions, and a translational fusion, SKN-1 is shown to become highly active in the C. elegans intestine upon exposure to the human bacterial pathogens, Enterococcus faecalis and Pseudomonas aeruginosa. Activation is dependent on the overall pathogenicity of the bacterium, demonstrated by a weakened response observed in attenuated mutants of these pathogens. Previous work demonstrated a role for p38 MAPK signaling both in pathogen resistance and in activating SKN-1 upon exposure to chemically induced oxidative stress. We show that NSY-1, SEK-1 and PMK-1 are also required for SKN-1 activity during infection. Evidence is also presented that the ROS produced by Ce-Duox1/BLI-3 is the source of SKN-1 activation via p38 MAPK signaling during infection. Finally, for the first time, SKN-1 activity is shown to be protective during infection; loss of skn-1 decreases resistance, whereas increasing SKN-1 activity augments resistance to pathogen. Overall, a model is presented in which ROS generation by Ce-Duox1/BLI-3 activates a protective SKN-1 response via p38 MAPK signaling.

Vyšlo v časopise: Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002453
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002453

Souhrn

Zdroje

1. BedardKKrauseKH 2007 The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87 245 313

2. LambethJDKawaharaTDieboldB 2007 Regulation of Nox and Duox enzymatic activity and expression. Free Radic Biol Med 43 319 331

3. ChavezVMohri-ShiomiAGarsinDA 2009 Ce-Duox1/BLI-3 generates reactive oxygen species as a protective innate immune mechanism in Caenorhabditis elegans. PMCID: 2772517. Infect Immun 77 4983 4989

4. EdensWASharlingLChengGShapiraRKinkadeJM 2001 Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. J Cell Biol 154 879 891

5. JainCYunMPolitzSMRaoRP 2009 A pathogenesis assay using Saccharomyces cerevisiae and Caenorhabditis elegans reveals novel roles for yeast AP-1, Yap1, and host dual oxidase BLI-3 in fungal pathogenesis. Eukaryot Cell 8 1218 1227

6. ChavezVMohri-ShiomiAMaadaniAVegaLAGarsinDA 2007 Oxidative stress enzymes are required for DAF-16-mediated immunity due to generation of reactive oxygen species by Caenorhabditis elegans. Genetics 176 1567 1577

7. Mohri-ShiomiAGarsinDA 2008 Insulin Signaling and the Heat Shock Response Modulate Protein Homeostasis in the Caenorhabditis elegans Intestine during Infection. J Biol Chem 283 194 201

8. AnJHBlackwellTK 2003 SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17 1882 1893

9. XuCLiCYKongAN 2005 Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 28 249 268

10. OliveiraRPPorter AbateJDilksKLandisJAshrafJ 2009 Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell 8 524 541

11. ParkSKTedescoPMJohnsonTE 2009 Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8 258 269

12. InoueHHisamotoNAnJHOliveiraRPNishidaE 2005 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19 2278 2283

13. KimDHFeinbaumRAlloingGEmersonFEGarsinDA 2002 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297 623 626

14. LiberatiNTFitzgeraldKAKimDHFeinbaumRGolenbockDT 2004 Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci U S A 101 6593 6598

15. ShiversRPPaganoDJKooistraTRichardsonCEReddyKC 2010 Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS Genet 6 e1000892

16. HayakawaTKatoKHayakawaRHisamotoNMatsumotoK 2011 Regulation of Anoxic Death in Caenorhabditis elegans by Mammalian Apoptosis Signal-regulating Kinase (ASK) Family Proteins. Genetics 187 785 792

17. KondoMYanaseSIshiiTHartmanPSMatsumotoK 2005 The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Caenorhabditis elegans nuclei. Mech Ageing Dev 126 642 647

18. LiXMatilainenOJinCGlover-CutterKMHolmbergCI 2011 Specific SKN-1/Nrf Stress Responses to Perturbations in Translation Elongation and Proteasome Activity. PLoS Genet 7 e1002119

19. KawliTWuCTanMW 2010 Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans. Proc Natl Acad Sci U S A 107 13788 13793

20. TulletJMHertweckMAnJHBakerJHwangJY 2008 Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132 1025 1038

21. LeiersBKampkotterAGreveldingCGLinkCDJohnsonTE 2003 A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radic Biol Med 34 1405 1415

22. WangJRobida-StubbsSTulletJMRualJFVidalM 2010 RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS Genet 6 e1001048

23. TanMWMahajan-MiklosSAusubelFM 1999 Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A 96 715 720

24. ReimmannCBeyelerMLatifiAWintelerHFoglinoM 1997 The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24 309 319

25. LauGWHassettDJRanHKongF 2004 The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med 10 599 606

26. Price-WhelanADietrichLENewmanDK 2006 Rethinking 'secondary' metabolism: physiological roles for phenazine antibiotics. Nat Chem Biol 2 71 78

27. RadaBLekstromKDamianSDupuyCLetoTL 2008 The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells. J Immunol 181 4883 4893

28. Mahajan-MiklosSTanMWRahmeLGAusubelFM 1999 Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96 47 56

29. MavrodiDVBonsallRFDelaneySMSouleMJPhillipsG 2001 Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1. J Bacteriol 183 6454 6465

30. GarsinDASifriCDMylonakisEQinXSinghKV 2001 A simple model host for identifying Gram-positive virulence factors. Proc Natl Acad Sci U S A 98 10892 10897

31. SifriCDMylonakisESinghKVQinXGarsinDA 2002 Virulence effect of Enterococcus faecalis protease genes and the quorum-sensing locus fsr in Caenorhabditis elegans and mice. Infect Immun 70 5647 5650

32. BowermanBDraperBWMelloCCPriessJR 1993 The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos. Cell 74 443 452

33. AballayAYorgeyPAusubelFM 2000 Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans. Curr Biol 10 1539 1542

34. MiyataSBegunJTroemelERAusubelFM 2008 DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics 178 903 918

35. BowermanBEatonBAPriessJR 1992 skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo. Cell 68 1061 1075

36. IrazoquiJENgAXavierRJAusubelFM 2008 Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions. Proc Natl Acad Sci U S A 105 17469 17474

37. ShapiraMHamlinBJRongJChenKRonenM 2006 A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci U S A 103 14086 14091

38. AballayA 2009 Neural regulation of immunity: role of NPR-1 in pathogen avoidance and regulation of innate immunity. Cell Cycle 8 966 969

39. AnJHVranasKLuckeMInoueHHisamotoN 2005 Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3. Proc Natl Acad Sci U S A 102 16275 16280

40. ChoeKPPrzybyszAJStrangeK 2009 The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Mol Cell Biol 29 2704 2715

41. WoodsCGFuJXuePHouYPlutaLJ 2009 Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages. Toxicol Appl Pharmacol 238 27 36

42. KellAVenturaNKahnNJohnsonTE 2007 Activation of SKN-1 by novel kinases in Caenorhabditis elegans. Free Radic Biol Med 43 1560 1566

43. KimDHLiberatiNTMizunoTInoueHHisamotoN 2004 Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase. Proc Natl Acad Sci U S A 101 10990 10994

44. LiuHNishitohHIchijoHKyriakisJM 2000 Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor-associated factor 2 requires prior dissociation of the ASK1 inhibitor thioredoxin. Mol Cell Biol 20 2198 2208

45. SaitohMNishitohHFujiiMTakedaKTobiumeK 1998 Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17 2596 2606

46. MatsuzawaASaegusaKNoguchiTSadamitsuCNishitohH 2005 ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol 6 587 592

47. TheinMCWinterADStepekGMcCormackGStapletonG 2009 Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in Caenorhabditis elegans. J Biol Chem 284 17549 17563

48. KumarSMolina-CruzAGuptaLRodriguesJBarillas-MuryC 2010 A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae. Science 327 1644 1648

49. FortezaRSalatheMMiotFFortezaRConnerGE 2005 Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol 32 462 469

50. GeisztMWittaJBaffiJLekstromKLetoTL 2003 Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. Faseb J 17 1502 1504

51. HopeIA 1999 C. elegans A Practical Approach. HamesBD Oxford: Oxford University Press

52. BrennerS 1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94

53. DunnyGMBrownBLClewellDB 1978 Induced cell aggregation and mating in Streptococcus faecalis: evidence for a bacterial sex pheromone. Proc Natl Acad Sci U S A 75 3479 3483

54. FraserAGKamathRSZipperlenPMartinez-CamposMSohrmannM 2000 Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408 325 330

55. KamathRSFraserAGDongYPoulinGDurbinR 2003 Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421 231 237

56. TimmonsLCourtDLFireA 2001 Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263 103 112

57. GarsinDAVillanuevaJMBegunJKimDHSifriCD 2003 Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300 1921