Blood Feeding and Insulin-like Peptide 3 Stimulate Proliferation of Hemocytes in the Mosquito

English version České info

All vector mosquito species must feed on the blood of a vertebrate host to produce eggs. Multiple cycles of blood feeding also promote frequent contacts with hosts, which enhance the risk of exposure to infectious agents and disease transmission. Blood feeding triggers the release of insulin-like peptides (ILPs) from the brain of the mosquito Aedes aegypti, which regulate blood meal digestion and egg formation. In turn, hemocytes serve as the most important constitutive defense in mosquitoes against pathogens that enter the hemocoel. Prior studies indicated that blood feeding stimulates hemocytes to increase in abundance, but how this increase in abundance is regulated is unknown. Here, we determined that phagocytic granulocytes and oenocytoids express the A. aegypti insulin receptor (AaMIR). We then showed that: 1) decapitation of mosquitoes after blood feeding inhibited hemocyte proliferation, 2) a single dose of insulin-like peptide 3 (ILP3) sufficient to stimulate egg production rescued proliferation, and 3) knockdown of the AaMIR inhibited ILP3 rescue activity. Infection studies indicated that increased hemocyte abundance enhanced clearance of the bacterium Escherichia coli at lower levels of infection. Surprisingly, however, non-blood fed females better survived intermediate and high levels of E. coli infection than blood fed females. Taken together, our results reveal a previously unrecognized role for the insulin signaling pathway in regulating hemocyte proliferation. Our results also indicate that blood feeding enhances resistance to E. coli at lower levels of infection but reduces tolerance at higher levels of infection.

Vyšlo v časopise: Blood Feeding and Insulin-like Peptide 3 Stimulate Proliferation of Hemocytes in the Mosquito. PLoS Pathog 7(10): e32767. doi:10.1371/journal.ppat.1002274
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002274

Souhrn

Zdroje

1. SieglaffDHDuncanKABrownMR 2005 Expression of genes encoding proteins involved in ecdysteroidogenesis in the female mosquito, Aedes aegypti. Insect Biochem Mol Biol 3 471 490

2. BrownMRClarkKDGuliaMZhaoZGarczynskiSF 2008 An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti. Proc Natl Acad Sci USA 105 5716 5721

3. WenZGuliaMClarkKDDharaACrimJW 2010 Two insulin-like peptide family members from the mosquito Aedes aegypti exhibit differential biological and receptor binding activities. Mol Cell Endocrinol 328 47 55

4. BrandonMCPenningtonJEIsoeJZamoraJSchillingerAS 2008 TOR signaling is required for amino acid stimulation of early trypsin protein synthesis in the midgut of Aedes aegypti mosquitoes. Insect Biochem Mol Biol 38 916 922

5. IsoeJRascónAAJrKunzSMiesfeldRL 2009 Molecular genetic analysis of midgut serine proteases in Aedes aegypti mosquitoes. Insect Biochem Mol Biol 39 903 912

6. Gulia-NussMRobertsonAEBrownMRStrandMR 2011 Insulin-like peptides and the Target of Rapamycin pathway coordinately regulate blood digestion and egg maturation in the mosquito Aedes aegypti. Plos One 6 e20401

7. AttardoGMHansenIARaikhelAS 2005 Nutritional regulation of vitellogenesis in mosquitoes: implications for anautogeny. Insect Biochem Mol Biol 35 661 675

8. RoySGHansenIARaikhelAS 2007 Effect of insulin and 20-hydroxyecdysone in the fat body of the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 37 1317 1326

9. HaineERMoretYSiva-JothyMTRolffJ 2008 Antimicrobial defense and persistent infection in insects. Science 322 1257 1259

10. StrandMR 2008 Insect hemocytes and their role in immunity. BeckageNE Insect Immunology San Diego Academic Press 25 48

11. HillyerJF 2009 Transcription in mosquito hemocytes in response to pathogen exposure. J Biol 8 e51

12. HillyerJFSchmidtSLChristensenBM 2003 Rapid phagocytosis and melanization of bacteria and Plasmodium sporozoites by hemocytes of the mosquito Aedes aegypti. J Parasitol 89 62 69

13. HillyerJFSchmidtSLFuchsJFBoyleJPChristensenBM 2005 Age-associated mortality in immune challenged mosquitoes (Aedes aegypti) correlates with a decrease in haemocyte numbers. Cell Microbiol 7 39 51

14. MoitaLFWang-SattlerRMichelKZimmermannTBlandinS 2005 In vivo identification of novel regulators and conserved pathways of phagocytosis in A. gambiae. Immunity 23 65 73

15. CastilloJCRobertsonAEStrandMR 2006 Characterization of hemocytes from the mosquitoes Anopheles gambiae and Aedes aegypti. Insect Biochem Mol Biol 36 891 903

16. MoitaCSimõesSMoitaLFJacintoAFernandesP 2005 The cadherin superfamily in Anopheles gambiae: a comparative study with Drosophila melanogaster. Comp Funct Genomics 6 204 216

17. BatonLARobertsonAWarrEStrandMRDimopoulosG 2009 Genome-wide transcriptomic profiling of Anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and Plasmodium berghei infection. BMC Genomics 10 257

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

19. VlachouDSchlegelmilchTChristophidesGKKafatosFC 2005 Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. Curr Biol 15 1185 1195

20. AbrahamEGPintoSBGhoshAVanlanginghamDLBuddA 2005 An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites. Proc Natl Acad Sci U S A 102 16327 16332

21. BartholomayLCMayhewGFFuchsJFRocheleauTAEricksonSM 2007 Profiling infection responses in the haemocytes of the mosquito, Aedes aegypti. Insect Mol Biol 16 761 76

22. BlandinSAMaroisELevashinaEA 2008 Antimalarial responses in Anopheles gambiae: from a complement-like protein to a complement-like pathway. Cell Host Microbe 3 364 374

23. PintoSBLombardoFKoutsosACWaterhouseRMMcKayK 2009 Discovery of Plasmodium modulators by genome-wide analysis of circulating hemocytes in Anopheles gambiae. Proc Natl Acad Sci U S A 106 21270 21275

24. RodriguesJBraynerFAAlvesLCDixitRBarillas-MuryC 2010 Hemocyte differentiation mediates innate immune memory in Anopheles gambiae mosquitoes. Science 329 1353 1355

25. LavineMDStrandMR 2003 Haemocytes from Pseudoplusia includens express multiple alpha and beta integrin subunits. Insect Mol Biol 12 441 452

26. GardinerEMStrandMR 1999 Monoclonal antibodies bind distinct classes of hemocytes in the moth Pseudoplusia includens. J Insect Physiol 45 113 126

27. GrafRLeaAOBriegelH 1998 A temporal profile of the endocrine control of trypsin synthesis in the yellow fever mosquito, Aedes aegypti. J Insect Physiol 44 451 454

28. RiehleMAFanYCaoCBrownMR 2006 Molecular characterization of insulin-like peptides in the yellow fever mosquito Aedes aegypti: expression, cellular localization, and phylogeny. Peptides 27 2547 2560

29. TrumanJWBateM 1988 Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol 125 145 157

30. GardinerEMMStrandMR 2000 Hematopoiesis in larval Pseudoplusia includens and Spodoptera frugiperda. Arch Insect Biochem Physiol 43 147 164

31. GordonSDStrandMR 2009 The polyembryonic wasp Copidosoma floridanum produces two castes by differentially parceling the germ line to daughter embryos during embryo proliferation. Dev Genes Evol 219 445 454

32. LowenbergerC 2001 Innate immune response of Aedes aegypti. Insect Biochem Mol Biol 31 219 229

33. BartholomayLCWaterhouseRMMayhewGFCampbellCLMichelK 2010 Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens. Science 330 88 90

34. ChristensenBMFortonKF 1986 Hemocyte-mediated melanization of microfilariae in Aedes aegypti. J Parasitol 72 220 225

35. HuberMCabibEMillerLH 1991 Malaria parasite chitinase and penetration of the mosquito peritrophic membrane. Proc Natl Acad Sci U S A 88 2807 2810

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

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

38. MárkusRLaurinyeczBKuruczEHontiVBajuszI 2009 Sessile hemocytes as a hematopoietic compartment in Drosophila melanogaster. Proc Natl Acad Sci USA 106 4805 4809

39. NakaharaYMatsumotoHKanamoriYKataokaHMizoguchiA 2006 Insulin signaling is involved in hematopoietic regulation in an insect hematopoietic organ. J Insect Physiol 52 105 111

40. WebsterJITonelliLSternbergEM 2002 Neuroendocrine regulation of immunity. Ann Rev Immunol 20 125 163

41. WhelanJTLudwigDLBertrandFE 2008 HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute lymphoblastic leukemia. Leukemia 22 1161 1169

42. NagatomoTMutaKOhgaSOchiaiMOhshimaK 2008 Insulin-like growth factor-II: a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors. Exp Hematol 36 401 11

43. LinXSöderhällKSöderhällI 2011 Invertebrate hematopoiesis: an astakine-dependent novel hematopoietic factor. J Immunol 186 2073 2079

44. GlassCKOgawaS 2006 Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6 44 55

45. ChowEKHRazaniBChengG 2007 Innate immune system regulation of nuclear hormone receptors in metabolic diseases. J Leukoc Biol 82 187 195

46. MüllerHMDimopoulosGBlassCKafatosFC 1999 A hemocyte-like cell line established from the malaria vector Anopheles gambiae expresses six prophenoloxidase genes. J Biol Chem 274 11727 11735

47. SilvermanNZhouRStövenSPandeyNHultmarkD 2000 A Drosophila IκB kinase complex required for Relish cleavage and antibacterial immunity. Genes Dev 14 2461 2471

48. FlattTHeylandARusFPorpigliaESherlockC 2008 Hormonal regulation of the humoral innate immune response in Drosophila melanogaster. J Exp Biol 211 2712 24

49. DimarcqJLImlerJLLanotREzekowitzRABHoffmanJA 1997 Treatment of I(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression. Insect Biochem Mol Biol 27 877 886

50. LanotRZacharyDHolderFMeisterM 2001 Postembryonic hematopoiesis in Drosophila. Dev Biol 230 243 257

51. SchneiderDSAyresJS 2008 Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol 8 889 895

52. Corby-HarrisVHabelKEAliFGPromislowDE 2007 Alternative measures of response to Pseudomonas aeruginosa infection in Drosophila melanogaster. J Evol Biol 20 526 533

53. RåbergLSimDReadAF 2007 Disentangling genetic variation for resistance and tolerance to infectious diseases in animals. Science 318 812 814

54. AyersJSSchneiderDS 2008 A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections. PLoS Biol 6 2764 2773

55. DionneMSPhamLNShirasu-HizaMSchneiderDS 2006 Akt and foxo dysregulation contribute to infection-induced wasting in Drosophila. Curr Biol 16 1977 1985

56. DiAngeloJRBlandMLBambinaSCherrySBirnbaumMJ 2009 The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc Natl Acad Sci U S A 106 20853 20858

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

58. ZhouGScaraffiaPYWellsMA 2005 Vector nutrition and energy metabolism. MarquardtWC Biology of disease vectors New York Elsevier 311 327

59. OliveiraJHMGoncalvesRLSLaraFADiasFAGandaraACP 2011 Blood meal-derived heme decreases ROS levels in the midgut of Aedes aegypti and allows proliferation of intestinal microbiota. PLoS Path 7 e1001320