Engineered Immunity to Infection


A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.


Vyšlo v časopise: Engineered Immunity to Infection. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002458
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002458

Souhrn

A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.


Zdroje

1. CirimotichCMDongYGarverLSSimSDimopoulosG 2010 Mosquito immune defenses against Plasmodium infection. Dev Comp Immunol 34 387 395

2. MeisterSKoutsosACChristophidesGK 2004 The Plasmodium parasite-a ‘new’ challenge for insect innate immunity. Int J Parasitol 34 1473 1482

3. MichelKKafatosFC 2005 Mosquito immunity against Plasmodium. Insect Biochem Mol Biol 35 677 689

4. GarverLSDongYDimopoulosG 2009 Caspar controls resistance to Plasmodium falciparum in diverse anopheline species. PLoS Pathog 5 e1000335

5. MitriCJacquesJCThieryIRiehleMMXuJ 2009 Fine pathogen discrimination within the APL1 gene family protects Anopheles gambiae against human and rodent malaria species. PLoS Pathog 5 e1000576

6. DongYDimopoulosG 2009 Anopheles fibrinogen-related proteins provide expanded pattern recognition capacity against bacteria and malaria parasites. J Biol Chem 284 9835 9844

7. RiehleMMXuJLazzaroBPRottschaeferSMCoulibalyB 2008 Anopheles gambiae APL1 is a family of variable LRR proteins required for Rel1-mediated protection from the malaria parasite, Plasmodium berghei. PLoS One 3 e3672

8. PovelonesMWaterhouseRMKafatosFCChristophidesGK 2009 Leucine-rich repeat protein complex activates mosquito complement in defense against Plasmodium parasites. Science 324 258 261

9. MeisterSKanzokSMZhengXLLunaCLiTR 2005 Immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito Anopheles gambiae. Proc Natl Acad Sci U S A 102 11420 11425

10. DongYAguilarRXiZWarrEMonginE 2006 Anopheles gambiae immune responses to human and rodent Plasmodium parasite species. PLoS Pathog 2 e52

11. BlandinSShiaoSHMoitaLFJanseCJWatersAP 2004 Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell 116 661 670

12. RottschaeferSMRiehleMMCoulibalyBSackoMNiareO 2011 Exceptional diversity, maintenance of polymorphism, and recent directional selection on the APL1 malaria resistance genes of Anopheles gambiae. PLoS Biol 9 e1000600

13. AntonovaYAlvarezKSKimYJKokozaVRaikhelAS 2009 The role of NF-kappaB factor REL2 in the Aedes aegypti immune response. Insect Biochem Mol Biol 39 303 314

14. ItoJGhoshAMoreiraLAWimmerEAJacobs-LorenaM 2002 Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417 452 455

15. NirmalaXMarinottiOSandovalJMPhinSGakharS 2006 Functional characterization of the promoter of the vitellogenin gene, AsVg1, of the malaria vector, Anopheles stephensi. Insect Biochem Mol Biol 36 694 700

16. HornCWimmerEA 2000 A versatile vector set for animal transgenesis. Dev Genes Evol 210 630 637

17. ChenCHHuangHWardCMSuJTSchaefferLV 2007 A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila. Science 316 597 600

18. WindbichlerNMenichelliMPapathanosPAThymeSBLiH 2011 A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature 473 212 215

19. IsaacsATLiFJasinskieneNChenXNirmalaX 2011 Engineered Resistance to Plasmodium falciparum development in transgenic Anopheles stephensi. PLoS Pathog 7 e1002017

20. MeredithJMBasuSNimmoDDLarget-ThieryIWarrEL 2011 Site-specific integration and expression of an anti-malarial gene in transgenic Anopheles gambiae significantly reduces Plasmodium infections. PLoS One 6 e14587

21. VizioliJBuletPHoffmannJAKafatosFCMullerHM 2001 Gambicin: a novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae. Proc Natl Acad Sci U S A 98 12630 12635

22. BlandinSMoitaLFKocherTWilmMKafatosFC 2002 Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the defensin gene. EMBO Rep 3 852 856

23. FraitureMBaxterRHSteinertSChelliahYFroletC 2009 Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium. Cell Host Microbe 5 273 284

24. MeisterSAgianianBTurlureFRelogioAMorlaisI 2009 Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites. PLoS Pathog 5 e1000542

25. ShahabuddinM 1998 Plasmodium ookinete development in the mosquito midgut: a case of reciprocal manipulation. Parasitology 116 Suppl S83 93

26. ChenXGMarinottiOWhitmanLJasinskieneNJamesAA 2007 The Anopheles gambiae vitellogenin gene (VGT2) promoter directs persistent accumulation of a reporter gene product in transgenic Anopheles stephensi following multiple bloodmeals. Am J Trop Med Hyg 76 1118 1124

27. MoreiraLAItoJGhoshADevenportMZielerH 2002 Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes. J Biol Chem 277 40839 40843

28. YoshidaSShimadaYKondohDKouzumaYGhoshAK 2007 Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development. PLoS Pathog 3 e192

29. KokozaVAhmedAWoon ShinSOkaforNZouZ 2010 Blocking of Plasmodium transmission by cooperative action of Cecropin A and Defensin A in transgenic Aedes aegypti mosquitoes. Proc Natl Acad Sci U S A 107 8111 8116

30. SindenREAlaviYRaineJD 2004 Mosquito--malaria interactions: a reappraisal of the concepts of susceptibility and refractoriness. Insect Biochem Mol Biol 34 625 629

31. ChurcherTSDawesEJSindenREChristophidesGKKoellaJC 2010 Population biology of malaria within the mosquito: density-dependent processes and potential implications for transmission-blocking interventions. Malar J 9 311

32. Corby-HarrisVDrexlerAWatkins de JongLAntonovaYPakpourN 2010 Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in Anopheles stephensi mosquitoes. PLoS Pathog 6 e1001003

33. FroletCThomaMBlandinSHoffmannJALevashinaEA 2006 Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei. Immunity 25 677 685

34. DimopoulosGMullerHMLevashinaEAKafatosFC 2001 Innate immune defense against malaria infection in the mosquito. Curr Opin Immunol 13 79 88

35. HoffmannJAReichhartJM 2002 Drosophila innate immunity: an evolutionary perspective. Nat Immunol 3 121 126

36. RaniASharmaARajagopalRAdakTBhatnagarRK 2009 Bacterial diversity analysis of larvae and adult midgut microflora using culture-dependent and culture-independent methods in lab-reared and field-collected Anopheles stephensi-an Asian malarial vector. BMC Microbiol 9 96

37. DongYManfrediniFDimopoulosG 2009 Implication of the mosquito midgut microbiota in the defense against malaria parasites. PLoS Pathog 5 e1000423

38. CirimotichCMDongYClaytonAMSandifordSLSouza-NetoJA 2011 Natural microbe-mediated refractoriness to Plasmodium infection in Anopheles gambiae. Science 332 855 858

39. ArmitageSAThompsonJJRolffJSiva-JothyMT 2003 Examining costs of induced and constitutive immune investment in Tenebrio molitor. J Evol Biol 16 1038 1044

40. LazzaroBPFloresHALoriganJGYourthCP 2008 Genotype-by-environment interactions and adaptation to local temperature affect immunity and fecundity in Drosophila melanogaster. PLoS Pathog 4 e1000025

41. KraaijeveldARGodfrayHC 1997 Trade-off between parasitoid resistance and larval competitive ability in Drosophila melanogaster. Nature 389 278 280

42. RonoMKWhittenMMOulad-AbdelghaniMLevashinaEAMaroisE 2010 The major yolk protein vitellogenin interferes with the anti-Plasmodium response in the malaria mosquito Anopheles gambiae. PLoS Biol 8 e1000434

43. LibertSChaoYChuXPletcherSD 2006 Trade-offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NF-kappaB signaling. Aging Cell 5 533 543

44. MoreiraLAWangJCollinsFHJacobs-LorenaM 2004 Fitness of anopheline mosquitoes expressing transgenes that inhibit Plasmodium development. Genetics 166 1337 1341

45. MarrelliMTMoreiraCKKellyDAlpheyLJacobs-LorenaM 2006 Mosquito transgenesis: what is the fitness cost? Trends Parasitol 22 197 202

46. MarrelliMTLiCRasgonJLJacobs-LorenaM 2007 Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood. Proc Natl Acad Sci U S A 104 5580 5583

47. LoboNFClaytonJRFraserMJKafatosFCCollinsFH 2006 High efficiency germ-line transformation of mosquitoes. Nat Protoc 1 1312 1317

48. CatterucciaFNolanTLoukerisTGBlassCSavakisC 2000 Stable germline transformation of the malaria mosquito Anopheles stephensi. Nature 405 959 962

49. TereniusOJuhnJJamesAA 2007 Injection of An.stephensi embryos to generate malaria-resistant mosquitoes. J Vis Exp 216

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

51. TalmanAMBlagboroughAMSindenRE 2010 A Plasmodium falciparum strain expressing GFP throughout the parasite's life-cycle. PLoS One 5 e9156

52. Franke-FayardBTruemanHRamesarJMendozaJvan der KeurM 2004 A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol Biochem Parasitol 137 23 33

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

54. DongYTaylorHEDimopoulosG 2006 AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles gambiae innate immune system. PLoS Biol 4 e229

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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2011 Číslo 12
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