#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Ubiquitin-Mediated Response to Microsporidia and Virus Infection in


Microbial pathogens have two distinct lifestyles:
some pathogens live outside of host cells, and others live inside of host cells and are called intracellular pathogens. Microsporidia are fungal-related intracellular pathogens that can infect all animals, but are poorly understood. We used the roundworm C. elegans as a host to show that ubiquitin pathways provide defense against both a natural microsporidian infection of C. elegans, as well as a natural viral infection. Our study shows that ubiquitin, the proteasome and autophagy components are all important to control intracellular infection in C. elegans, although microsporidia seem to partially evade this defense. We also show that SCF ubiquitin ligases help control both microsporidia and virus infection. Furthermore, we find that C. elegans upregulates expression of SCF ligases when ubiquitin-related degradation machinery is inhibited, indicating that C. elegans monitors the functioning of this core cellular process and upregulates ligase expression when it is perturbed. Altogether, our findings describe ubiquitin-mediated pathways that are involved in host response and defense against intracellular pathogens, and how this machinery is regulated by infection to increase defense against intracellular pathogens such as microsporidia and viruses.


Vyšlo v časopise: Ubiquitin-Mediated Response to Microsporidia and Virus Infection in. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004200
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004200

Souhrn

Microbial pathogens have two distinct lifestyles:
some pathogens live outside of host cells, and others live inside of host cells and are called intracellular pathogens. Microsporidia are fungal-related intracellular pathogens that can infect all animals, but are poorly understood. We used the roundworm C. elegans as a host to show that ubiquitin pathways provide defense against both a natural microsporidian infection of C. elegans, as well as a natural viral infection. Our study shows that ubiquitin, the proteasome and autophagy components are all important to control intracellular infection in C. elegans, although microsporidia seem to partially evade this defense. We also show that SCF ubiquitin ligases help control both microsporidia and virus infection. Furthermore, we find that C. elegans upregulates expression of SCF ligases when ubiquitin-related degradation machinery is inhibited, indicating that C. elegans monitors the functioning of this core cellular process and upregulates ligase expression when it is perturbed. Altogether, our findings describe ubiquitin-mediated pathways that are involved in host response and defense against intracellular pathogens, and how this machinery is regulated by infection to increase defense against intracellular pathogens such as microsporidia and viruses.


Zdroje

1. WilliamsBA (2009) Unique physiology of host-parasite interactions in microsporidia infections. Cellular microbiology 11: 1551–1560.

2. DidierES (2005) Microsporidiosis: an emerging and opportunistic infection in humans and animals. Acta tropica 94: 61–76.

3. DidierES, WeissLM (2011) Microsporidiosis: not just in AIDS patients. Current opinion in infectious diseases 24: 490–495.

4. HigesM, Martin-HernandezR, BotiasC, BailonEG, Gonzalez-PortoAV, et al. (2008) How natural infection by Nosema ceranae causes honeybee colony collapse. Environmental microbiology 10: 2659–2669.

5. KentML, SpeareDJ (2005) Review of the sequential development of Loma salmonae (Microsporidia) based on experimental infections of rainbow trout (Oncorhynchus mykiss) and Chinook salmon (O. tshawytscha). Folia parasitologica 52: 63–68.

6. TroemelER (2011) New models of microsporidiosis: infections in Zebrafish, C. elegans, and honey bee. PLoS pathogens 7: e1001243.

7. AnaneS, AttouchiH (2010) Microsporidiosis: epidemiology, clinical data and therapy. Gastroenterologie clinique et biologique 34: 450–464.

8. DidierES, MaddryJA, BrindleyPJ, StovallME, DidierPJ (2005) Therapeutic strategies for human microsporidia infections. Expert review of anti-infective therapy 3: 419–434.

9. ValencakovaA, HalanovaM (2012) Immune response to Encephalitozoon infection review. Comparative immunology, microbiology and infectious diseases 35: 1–7.

10. MorettoMM, KhanIA, WeissLM (2012) Gastrointestinal cell mediated immunity and the microsporidia. PLoS pathogens 8: e1002775.

11. Roxstrom-LindquistK, TereniusO, FayeI (2004) Parasite-specific immune response in adult Drosophila melanogaster: a genomic study. EMBO reports 5: 207–212.

12. TroemelER, FelixMA, WhitemanNK, BarriereA, AusubelFM (2008) Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans. PLoS Biol 6: 2736–2752.

13. HodgkinJ, PartridgeFA (2008) Caenorhabditis elegans meets microsporidia: the nematode killers from Paris. PLoS biology 6: 2634–2637.

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

15. FelixMA, AsheA, PiffarettiJ, WuG, NuezI, et al. (2011) Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLoS biology 9: e1000586.

16. LuR, MaduroM, LiF, LiHW, Broitman-MaduroG, et al. (2005) Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436: 1040–1043.

17. SarkiesP, AsheA, Le PenJ, McKieMA, MiskaEA (2013) Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans. Genome research 23: 1258–1270.

18. WilkinsC, DishonghR, MooreSC, WhittMA, ChowM, et al. (2005) RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436: 1044–1047.

19. AsheA, BelicardT, Le PenJ, SarkiesP, FrezalL, et al. (2013) A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. eLife 2: e00994.

20. CollinsCA, BrownEJ (2010) Cytosol as battleground: ubiquitin as a weapon for both host and pathogen. Trends in cell biology 20: 205–213.

21. HuettA, HeathRJ, BegunJ, SassiSO, BaxtLA, et al. (2012) The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium. Cell host & microbe 12: 778–790.

22. ManzanilloPS, AyresJS, WatsonRO, CollinsAC, SouzaG, et al. (2013) The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature 501: 512–516.

23. PerrinAJ, JiangX, BirminghamCL, SoNS, BrumellJH (2004) Recognition of bacteria in the cytosol of Mammalian cells by the ubiquitin system. Curr Biol 14: 806–811.

24. FangS, WeissmanAM (2004) A field guide to ubiquitylation. Cellular and molecular life sciences: CMLS 61: 1546–1561.

25. KnodlerLA, CelliJ (2011) Eating the strangers within: host control of intracellular bacteria via xenophagy. Cellular microbiology 13: 1319–1327.

26. Mansilla ParejaME, ColomboMI (2013) Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms. Frontiers in cellular and infection microbiology 3: 54.

27. BirminghamCL, BrumellJH (2006) Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles. Autophagy 2: 156–158.

28. BirminghamCL, SmithAC, BakowskiMA, YoshimoriT, BrumellJH (2006) Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. The Journal of biological chemistry 281: 11374–11383.

29. ThurstonTL, RyzhakovG, BloorS, von MuhlinenN, RandowF (2009) The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nature immunology 10: 1215–1221.

30. HuaZ, VierstraRD (2011) The cullin-RING ubiquitin-protein ligases. Annual review of plant biology 62: 299–334.

31. SkaarJR, PaganJK, PaganoM (2013) Mechanisms and function of substrate recruitment by F-box proteins. Nature reviews Molecular cell biology 14: 369–381.

32. ThomasJH (2006) Adaptive evolution in two large families of ubiquitin-ligase adapters in nematodes and plants. Genome Res 16: 1017–1030.

33. NayakS, SantiagoFE, JinH, LinD, SchedlT, et al. (2002) The Caenorhabditis elegans Skp1-related gene family: diverse functions in cell proliferation, morphogenesis, and meiosis. Current biology: CB 12: 277–287.

34. CuomoCA, DesjardinsCA, BakowskiMA, GoldbergJ, MaAT, et al. (2012) Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth. Genome research 22: 2478–2488.

35. EngelmannI, GriffonA, TichitL, Montanana-SanchisF, WangG, et al. (2011) A comprehensive analysis of gene expression changes provoked by bacterial and fungal infection in C. elegans. PLoS One 6: e19055.

36. HuffmanDL, AbramiL, SasikR, CorbeilJ, van der GootFG, et al. (2004) Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins. Proceedings of the National Academy of Sciences of the United States of America 101: 10995–11000.

37. 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 pathogens 6: e1000982.

38. MongkoldhumrongkulN, SwainSC, JayasingheSN, SturzenbaumS (2010) Bio-electrospraying the nematode Caenorhabditis elegans: studying whole-genome transcriptional responses and key life cycle parameters. Journal of the Royal Society, Interface/the Royal Society 7: 595–601.

39. MurphyCT, McCarrollSA, BargmannCI, FraserA, KamathRS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424: 277–283.

40. ShinH, LeeH, FejesAP, BaillieDL, KooHS, et al. (2011) Gene expression profiling of oxidative stress response of C. elegans aging defective AMPK mutants using massively parallel transcriptome sequencing. BMC research notes 4: 34.

41. TroemelER, ChuSW, ReinkeV, LeeSS, AusubelFM, et al. (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS genetics 2: e183.

42. SubramanianA, TamayoP, MoothaVK, MukherjeeS, EbertBL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America 102: 15545–15550.

43. KourtisN, NikoletopoulouV, TavernarakisN (2012) Small heat-shock proteins protect from heat-stroke-associated neurodegeneration. Nature 490: 213–218.

44. SinghV, AballayA (2006) Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proceedings of the National Academy of Sciences of the United States of America 103: 13092–13097.

45. Huang daW, ShermanBT, LempickiRA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature protocols 4: 44–57.

46. Huang daW, ShermanBT, LempickiRA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic acids research 37: 1–13.

47. BoxemM, TsaiCW, ZhangY, SaitoRM, LiuJO (2004) The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell proliferation. FEBS letters 576: 245–250.

48. MitchellDH, StilesJW, SantelliJ, SanadiDR (1979) Synchronous growth and aging of Caenorhabditis elegans in the presence of fluorodeoxyuridine. Journal of gerontology 34: 28–36.

49. BaileyL (1953) Effect of fumagillin upon Nosema apis (Zander). Nature 171: 212–213.

50. KatinkaMD, DupratS, CornillotE, MetenierG, ThomaratF, et al. (2001) Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414: 450–453.

51. SinN, MengL, WangMQ, WenJJ, BornmannWG, et al. (1997) The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings of the National Academy of Sciences of the United States of America 94: 6099–6103.

52. WilliamsGR, SampsonMA, ShutlerD, RogersRE (2008) Does fumagillin control the recently detected invasive parasite Nosema ceranae in western honey bees (Apis mellifera)? Journal of invertebrate pathology 99: 342–344.

53. HansenM, ChandraA, MiticLL, OnkenB, DriscollM, et al. (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS genetics 4: e24.

54. Manil-SegalenM, LefebvreC, JenzerC, TrichetM, BoulogneC, et al. (2014) The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. Developmental cell 28: 43–55.

55. KlionskyDJ, AbeliovichH, AgostinisP, AgrawalDK, AlievG, et al. (2008) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4: 151–175.

56. DunbarTL, YanZ, BallaKM, SmelkinsonMG, TroemelER (2012) C. elegans detects pathogen-induced translational inhibition to activate immune signaling. Cell host & microbe 11: 375–386.

57. 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.

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

59. GuisbertE, CzyzDM, RichterK, McMullenPD, MorimotoRI (2013) Identification of a tissue-selective heat shock response regulatory network. PLoS genetics 9: e1003466.

60. LiX, MatilainenO, JinC, Glover-CutterKM, HolmbergCI, et al. (2011) Specific SKN-1/Nrf stress responses to perturbations in translation elongation and proteasome activity. PLoS genetics 7: e1002119.

61. HorvathCM (2004) Weapons of STAT destruction. Interferon evasion by paramyxovirus V protein. European journal of biochemistry/FEBS 271: 4621–4628.

62. KomuroA, BammingD, HorvathCM (2008) Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Cytokine 43: 350–358.

63. RandowF, LehnerPJ (2009) Viral avoidance and exploitation of the ubiquitin system. Nature cell biology 11: 527–534.

64. RajsbaumR, Garcia-SastreA (2013) Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways. Trends in microbiology 21: 421–429.

65. ChoiAG, WongJ, MarchantD, LuoH (2013) The ubiquitin-proteasome system in positive-strand RNA virus infection. Reviews in medical virology 23: 85–96.

66. IrazoquiJE, UrbachJM, AusubelFM (2010) Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nature reviews Immunology 10: 47–58.

67. CouillaultC, PujolN, ReboulJ, SabatierL, GuichouJF, et al. (2004) TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nature immunology 5: 488–494.

68. 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 research 16: 1005–1016.

69. ShapiraM, HamlinBJ, RongJ, ChenK, RonenM, et al. (2006) A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proceedings of the National Academy of Sciences of the United States of America 103: 14086–14091.

70. KleinoA, SilvermanN (2012) UnZIPping mechanisms of effector-triggered immunity in animals. Cell host & microbe 11: 320–322.

71. LiuY, SamuelBS, BreenPC, RuvkunG (2014) Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508: 406–410.

72. StuartLM, PaquetteN, BoyerL (2013) Effector-triggered versus pattern-triggered immunity: how animals sense pathogens. Nature reviews Immunology 13: 199–206.

73. LemaitreB, GirardinSE (2013) Translation inhibition and metabolic stress pathways in the host response to bacterial pathogens. Nature reviews Microbiology 11: 365–369.

74. PowersET, BalchWE (2013) Diversity in the origins of proteostasis networks–a driver for protein function in evolution. Nature reviews Molecular cell biology 14: 237–248.

75. AballayA (2013) Role of the nervous system in the control of proteostasis during innate immune activation: insights from C. elegans. PLoS pathogens 9: e1003433.

76. TaylorRC, BerendzenKM, DillinA (2014) Systemic stress signalling: understanding the cell non-autonomous control of proteostasis. Nature reviews Molecular cell biology 15: 211–217.

77. AltoNM, OrthK (2012) Subversion of cell signaling by pathogens. Cold Spring Harbor perspectives in biology 4: a006114.

78. Steele-MortimerO (2011) Exploitation of the ubiquitin system by invading bacteria. Traffic 12: 162–169.

79. WullschlegerS, LoewithR, HallMN (2006) TOR signaling in growth and metabolism. Cell 124: 471–484.

80. ZhengYT, ShahnazariS, BrechA, LamarkT, JohansenT, et al. (2009) The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. Journal of immunology 183: 5909–5916.

81. AndersonDM, FrankDW (2012) Five mechanisms of manipulation by bacterial effectors: a ubiquitous theme. PLoS pathogens 8: e1002823.

82. VeigaE, CossartP (2005) Ubiquitination of intracellular bacteria: a new bacteria-sensing system? Trends in cell biology 15: 2–5.

83. PilarAV, Reid-YuSA, CooperCA, MulderDT, CoombesBK (2012) GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1. PLoS pathogens 8: e1002773.

84. Ardila-GarciaAM, FastNM (2012) Microsporidian infection in a free-living marine nematode. Eukaryotic cell 11: 1544–1551.

85. FelixMA, DuveauF (2012) Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae. BMC biology 10: 59.

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

87. EstesKA, SzumowskiSC, TroemelER (2011) Non-lytic, actin-based exit of intracellular parasites from C. elegans intestinal cells. PLoS pathogens 7: e1002227.

88. MelendezA, TalloczyZ, SeamanM, EskelinenEL, HallDH, et al. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301: 1387–1391.

89. KangC, YouYJ, AveryL (2007) Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes & development 21: 2161–2171.

90. ParkhomchukD, BorodinaT, AmstislavskiyV, BanaruM, HallenL, et al. (2009) Transcriptome analysis by strand-specific sequencing of complementary DNA. Nucleic acids research 37: e123.

91. LevinJZ, YassourM, AdiconisX, NusbaumC, ThompsonDA, et al. (2010) Comprehensive comparative analysis of strand-specific RNA sequencing methods. Nature methods 7: 709–715.

92. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome biology 10: R25.

93. LiB, DeweyCN (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC bioinformatics 12: 323.

94. RobinsonMD, McCarthyDJ, SmythGK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26: 139–140.

95. StoreyJD, TibshiraniR (2003) Statistical significance for genomewide studies. Proceedings of the National Academy of Sciences of the United States of America 100: 9440–9445.

96. HaenniS, JiZ, HoqueM, RustN, SharpeH, et al. (2012) Analysis of C. elegans intestinal gene expression and polyadenylation by fluorescence-activated nuclei sorting and 3'-end-seq. Nucleic acids research 40: 6304–6318.

97. WangX, ZhaoY, WongK, EhlersP, KoharaY, et al. (2009) Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE. BMC genomics 10: 213.

98. PfafflMW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic acids research 29: e45.

99. GuhaThakurtaD, PalomarL, StormoGD, TedescoP, JohnsonTE, et al. (2002) Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods. Genome research 12: 701–712.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#