The Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxification

English version České info

Metazoans respond to environmental threats in part through conserved pathways that coordinate protective transcriptional responses. During infection with an invasive pathogen, for example, innate immune pathways regulate the secretion of antimicrobial immune effectors. Likewise, exposure to toxic molecules leads to the induction of detoxification mechanisms that protect the host from the deleterious effects of these compounds. Here we find that a conserved transcriptional regulator MDT-15/MED15 links xenobiotic detoxification and immune responses in a manner that is important for protection during bacterial infection. We also show that MDT-15/MED15 is necessary for the host to resist the lethal effects of secreted toxins produced by pathogenic bacteria. Rapid coordination of these protective host responses through MDT-15/MED15 may therefore be part of a conserved survival strategy in the wild.

Vyšlo v časopise: The Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxification. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004143
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004143

Souhrn

Zdroje

1. LindblomTH, DoddAK (2006) Xenobiotic detoxification in the nematode Caenorhabditis elegans. J Exp Zoolog Part A Comp Exp Biol 305: 720–730.

2. Pukkila-WorleyR, AusubelFM (2012) Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium. Curr Opin Immunol 24: 3–9.

3. MeloJA, RuvkunG (2012) Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses. Cell 149: 452–466.

4. RunkelED, LiuS, BaumeisterR, SchulzeE (2013) Surveillance-activated defenses block the ROS-induced mitochondrial unfolded protein response. PLoS Genet 9: e1003346.

5. KimDH, FeinbaumR, AlloingG, EmersonFE, GarsinDA, et al. (2002) A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297: 623–626.

6. TroemelER, ChuSW, ReinkeV, LeeSS, AusubelFM, et al. (2006) p38 MAPK Regulates Expression of Immune Response Genes and Contributes to Longevity in C. elegans. PLoS Genet 2: e183.

7. Pukkila-WorleyR, AusubelFM, MylonakisE (2011) Candida albicans Infection of Caenorhabditis elegans Induces Antifungal Immune Defenses. PLoS Pathog 7: e1002074.

8. MoyTI, ConeryAL, Larkins-FordJ, WuG, MazitschekR, et al. (2009) High-throughput screen for novel antimicrobials using a whole animal infection model. ACS Chem Biol 4: 527–533.

9. Pukkila-WorleyR, FeinbaumR, KirienkoNV, Larkins-FordJ, ConeryAL, et al. (2012) Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection. PLoS Genet 8: e1002733.

10. BolzDD, TenorJL, AballayA (2010) A conserved PMK-1/p38 MAPK is required in Caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection. J Biol Chem 285: 10832–10840.

11. LiberatiNT, FitzgeraldKA, KimDH, FeinbaumR, GolenbockDT, et al. (2004) Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci USA 101: 6593–6598.

12. ShiversRP, PaganoDJ, KooistraT, RichardsonCE, ReddyKC, et al. (2010) Phosphorylation of the Conserved Transcription Factor ATF-7 by PMK-1 p38 MAPK Regulates Innate Immunity in Caenorhabditis elegans. PLoS Genet 6: e1000892.

13. LeeDG, UrbachJM, WuG, LiberatiNT, FeinbaumRL, et al. (2006) Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol 7: R90.

14. EstesKA, DunbarTL, PowellJR, AusubelFM, TroemelER (2010) bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans. Proc Natl Acad Sci USA 107: 2153–2158.

15. McEwanDL, KirienkoNV, AusubelFM (2012) Host Translational Inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an Immune Response in Caenorhabditis elegans. Cell Host Microbe 11: 364–374.

16. DunbarTL, YanZ, BallaKM, SmelkinsonMG, TroemelER (2012) C. elegans Detects Pathogen-Induced Translational Inhibition to Activate Immune Signaling. Cell Host Microbe 11: 375–386.

17. ShiversRP, KooistraT, ChuSW, PaganoDJ, KimDH (2009) Tissue-specific activities of an immune signaling module regulate physiological responses to pathogenic and nutritional bacteria in C. elegans. Cell Host Microbe 6: 321–330.

18. TaubertS, Van GilstMR, HansenM, YamamotoKR (2006) A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. Genes Dev 20: 1137–1149.

19. TaubertS, HansenM, Van GilstMR, CooperSB, YamamotoKR (2008) The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet 4: e1000021.

20. YangF, VoughtBW, SatterleeJS, WalkerAK, Jim SunZ-Y, et al. (2006) An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442: 700–704.

21. GohGYS, MartelliKL, ParharKS, KwongAWL, WongMA, et al. (2013) The conserved Mediator subunit MDT-15 is required for oxidative stress responses in C. elegans. Aging Cell 13(1): 70–9.

22. WongD, BazopoulouD, PujolN, TavernarakisN, EwbankJJ (2007) Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection. Genome Biol 8: R194.

23. O'RourkeD, BabanD, DemidovaM, MottR, HodgkinJ (2006) Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res 16: 1005–1016.

24. KimDH, LiberatiNT, MizunoT, InoueH, HisamotoN, et al. (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 USA 101: 10990–10994.

25. MiyataS, BegunJ, TroemelER, AusubelFM (2008) DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics 178: 903–918.

26. IrazoquiJE, TroemelER, FeinbaumRL, LuhachackLG, CezairliyanBO, et al. (2010) Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus. PLoS Pathog 6: e1000982.

27. FeinbaumRL, UrbachJM, LiberatiNT, DjonovicS, AdonizioA, et al. (2012) Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model. PLoS Pathog 8: e1002813.

28. CezairliyanB, VinayavekhinN, Grenfell-LeeD, YuenGJ, SaghatelianA, et al. (2013) Identification of Pseudomonas aeruginosa phenazines that kill Caenorhabditis elegans. PLoS Pathog 9: e1003101.

29. Mahajan-MiklosS, TanMW, RahmeLG, AusubelFM (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96: 47–56.

30. ConawayRC, ConawayJW (2011) Function and regulation of the Mediator complex. Curr Opin Genet Dev 21: 225–230.

31. MalikS, RoederRG (2010) The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet 11: 761–772.

32. HolstegeFC, JenningsEG, WyrickJJ, LeeTI, HengartnerCJ, et al. (1998) Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95: 717–728.

33. HuangS, HölzelM, KnijnenburgT, SchlickerA, RoepmanP, et al. (2012) MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling. Cell 151: 937–950.

34. BoyerTG, MartinME, LeesE, RicciardiRP, BerkAJ (1999) Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature 399: 276–279.

35. ThakurJK, ArthanariH, YangF, ChauKH, WagnerG, et al. (2009) Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p. J Biol Chem 284: 4422–4428.

36. ThakurJK, ArthanariH, YangF, PanS-J, FanX, et al. (2008) A nuclear receptor-like pathway regulating multidrug resistance in fungi. Nature 452: 604–609.

37. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.

38. GariganD, HsuA-L, FraserAG, KamathRS, AhringerJ, et al. (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161: 1101–1112.

39. McEwanDL, WeismanAS, HunterCP (2012) Uptake of extracellular double-stranded RNA by SID-2. Mol Cell 47: 746–754.

40. MelloCC, KramerJM, StinchcombD, AmbrosV (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J 10: 3959–3970.

41. KamathRS, AhringerJ (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30: 313–321.

42. RualJ-F, CeronJ, KorethJ, HaoT, NicotA-S, et al. (2004) Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 14: 2162–2168.

43. DietrichLEP, Price-WhelanA, PetersenA, WhiteleyM, NewmanDK (2006) The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol Microbiol 61: 1308–1321.

44. TanMW, Mahajan-MiklosS, AusubelFM (1999) Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci USA 96: 715–720.

45. PfafflMW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.