The events leading to a successful encapsulation of parasitoid wasp eggs in the larvae of the fruit fly Drosophila melanogaster are insufficiently understood. The formation of a capsule seals off the wasp egg, and this process is often functionally compared to the formation of granulomas in vertebrates. Like granuloma formation in humans, the encapsulation process in fruit flies requires the activation, mobilization, proliferation and differentiation of different blood cell types. Here, we have studied the role of Edin (elevated during infection) in the immune defense against the parasitoid wasp Leptopilina boulardi in Drosophila larvae. We demonstrate that edin expression in the fat body (an immune-responsive organ in Drosophila functionally resembling the mammalian liver) is required for a normal defense against wasp eggs. Edin is required for the release of blood cells from larval tissues and for the subsequent increase in circulating blood cell numbers. Our results provide new knowledge of how the encapsulation process is regulated in Drosophila, and how blood cells are activated upon wasp parasitism. Understanding of the encapsulation process in invertebrates may eventually lead to a better knowledge of the pathophysiology of granuloma formation in human diseases, such as tuberculosis.
Vyšlo v časopise: Expression in the Fat Body Is Required in the Defense Against Parasitic Wasps in. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004895 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004895
1. Keebaugh ES, Schlenke TA. Insights from natural host-parasite interactions: The drosophila model. Dev Comp Immunol 2014; 42(1): 111–123. doi: 10.1016/j.dci.2013.06.001 23764256
2. Benassi V, Coustau C, Carton Y. Insect immunity: A genetic factor (hrtp) is essential for antibacterial peptide expression in drosophila after infection by parasitoid wasps. Arch Insect Biochem Physiol 2000; 43(2): 64–71. 10644970
3. Schlenke TA, Morales J, Govind S, Clark AG. Contrasting infection strategies in generalist and specialist wasp parasitoids of drosophila melanogaster. PLoS Pathog 2007; 3(10): 1486–1501. 17967061
4. Wertheim B, Kraaijeveld AR, Schuster E, Blanc E, Hopkins M, et al. Genome-wide gene expression in response to parasitoid attack in drosophila. Genome Biol 2005; 6(11): R94. 16277749
5. Valanne S, Wang JH, Rämet M. The drosophila toll signaling pathway. J Immunol 2011; 186(2): 649–656. doi: 10.4049/jimmunol.1002302 21209287
6. Myllymäki H, Valanne S, Rämet M. The drosophila imd signaling pathway. J Immunol 2014; 192(8): 3455–3462. doi: 10.4049/jimmunol.1303309 24706930
7. Honti V, Csordas G, Kurucz E, Márkus R, Andó I. The cell-mediated immunity of drosophila melanogaster: Hemocyte lineages, immune compartments, microanatomy and regulation. Dev Comp Immunol 2014; 42(1): 47–56. doi: 10.1016/j.dci.2013.06.005 23800719
8. Meister M, Lagueux M. Drosophila blood cells. Cell Microbiol 2003; 5(9): 573–580. 12925127
9. Elrod-Erickson M, Mishra S, Schneider D. Interactions between the cellular and humoral immune responses in drosophila. Curr Biol 2000; 10(13): 781–784. 10898983
10. Franc NC, Heitzler P, Ezekowitz RA, White K. Requirement for croquemort in phagocytosis of apoptotic cells in drosophila. Science 1999; 284(5422): 1991–1994. 10373118
11. Manaka J, Kuraishi T, Shiratsuchi A, Nakai Y, Higashida H, et al. Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by drosophila hemocytes/macrophages. J Biol Chem 2004; 279(46): 48466–48476. 15342648
12. Ulvila J, Vanha-aho LM, Kleino A, Vähä-Mäkilä M, Vuoksio M, et al. Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance. J Leukoc Biol 2011; 89(5): 649–659. doi: 10.1189/jlb.0410195 21208897
13. Meister M. Blood cells of drosophila: Cell lineages and role in host defence. Curr Opin Immunol 2004; 16(1): 10–15. 14734104
14. Russo J, Dupas S, Frey F, Carton Y, Brehelin M. Insect immunity: Early events in the encapsulation process of parasitoid (leptopilina boulardi) eggs in resistant and susceptible strains of drosophila. Parasitology 1996; 112 (Pt 1)(Pt 1): 135–142. 8587797
15. Rizki TM, Rizki RM. Lamellocyte differentiation in drosophila larvae parasitized by leptopilina. Dev Comp Immunol 1992; 16(2–3): 103–110. 1473596
16. Stofanko M, Kwon SY, Badenhorst P. Lineage tracing of lamellocytes demonstrates drosophila macrophage plasticity. PLoS One 2010; 5(11): e14051. doi: 10.1371/journal.pone.0014051 21124962
17. Honti V, Csordas G, Márkus R, Kurucz E, Jankovics F, et al. Cell lineage tracing reveals the plasticity of the hemocyte lineages and of the hematopoietic compartments in drosophila melanogaster. Mol Immunol 2010; 47(11–12): 1997–2004. doi: 10.1016/j.molimm.2010.05.291 20691478
18. Nappi AJ, Vass E. Hydrogen peroxide production in immune-reactive drosophila melanogaster. J Parasitol 1998; 84(6): 1150–1157. 9920305
19. Verleyen P, Baggerman G, D'Hertog W, Vierstraete E, Husson SJ, et al. Identification of new immune induced molecules in the haemolymph of drosophila melanogaster by 2D-nanoLC MS/MS. J Insect Physiol 2006; 52(4): 379–388. 16510152
20. Vanha-aho LM, Kleino A, Kaustio M, Ulvila J, Wilke B, et al. Functional characterization of the infection-inducible peptide edin in drosophila melanogaster. PLoS One 2012; 7(5): e37153. doi: 10.1371/journal.pone.0037153 22606343
21. Gordon MD, Ayres JS, Schneider DS, Nusse R. Pathogenesis of listeria-infected drosophila wntD mutants is associated with elevated levels of the novel immunity gene edin. PLoS Pathog 2008; 4(7): e1000111. doi: 10.1371/journal.ppat.1000111 18654628
22. Harrison DA, Binari R, Nahreini TS, Gilman M, Perrimon N. Activation of a drosophila janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J 1995; 14(12): 2857–2865. 7796812
23. Williams MJ, Andó I, Hultmark D. Drosophila melanogaster Rac2 is necessary for a proper cellular immune response. Genes Cells 2005; 10(8): 813–823. 16098145
24. Russo J, Brehelin M, Carton Y. Haemocyte changes in resistant and susceptible strains of D. melanogaster caused by virulent and avirulent strains of the parasitic wasp leptopilina boulardi. J Insect Physiol 2001; 47(2): 167–172. 11064023
25. Zettervall CJ, Anderl I, Williams MJ, Palmer R, Kurucz E, et al. A directed screen for genes involved in drosophila blood cell activation. Proc Natl Acad Sci U S A 2004; 101(39): 14192–14197. 15381778
26. Márkus R, Laurinyecz B, Kurucz E, Honti V, Bajusz I, et al. Sessile hemocytes as a hematopoietic compartment in drosophila melanogaster. Proc Natl Acad Sci U S A 2009; 106(12): 4805–4809. doi: 10.1073/pnas.0801766106 19261847
27. Kacsoh BZ, Schlenke TA. High hemocyte load is associated with increased resistance against parasitoids in drosophila suzukii, a relative of D. melanogaster. PLoS One 2012; 7(4): e34721. doi: 10.1371/journal.pone.0034721 22529929
28. Moreau SJ, Guillot S, Populaire C, Doury G, Prevost G, et al. Conversely to its sibling drosophila melanogaster, D. simulans overcomes the immunosuppressive effects of the parasitoid asobara citri. Dev Comp Immunol 2005; 29(3): 205–209. 15572069
29. Prevost G, Eslin P. Hemocyte load and immune resistance to asobara tabida are correlated in species of the drosophila melanogaster subgroup. J Insect Physiol 1998; 44(9): 807–816. 12769876
30. Kraaijeveld AR, Hutcheson KA, Limentani EC, Godfray HC. Costs of counterdefenses to host resistance in a parasitoid of drosophila. Evolution 2001; 55(9): 1815–1821. 11681736
31. Lanot R, Zachary D, Holder F, Meister M. Postembryonic hematopoiesis in drosophila. Dev Biol 2001; 230(2): 243–257. 11161576
32. Stofanko M, Kwon SY, Badenhorst P. A misexpression screen to identify regulators of drosophila larval hemocyte development. Genetics 2008; 180(1): 253–267. doi: 10.1534/genetics.108.089094 18757933
33. Williams MJ, Wiklund ML, Wikman S, Hultmark D. Rac1 signalling in the drosophila larval cellular immune response. J Cell Sci 2006; 119(Pt 10): 2015–2024. 16621891
34. Williams MJ, Habayeb MS, Hultmark D. Reciprocal regulation of Rac1 and Rho1 in drosophila circulating immune surveillance cells. J Cell Sci 2007; 120(Pt 3): 502–511. 17227793
35. Narita R, Yamashita H, Goto A, Imai H, Ichihara S, et al. Syndecan-dependent binding of drosophila hemocytes to laminin alpha3/5 chain LG4-5 modules: Potential role in sessile hemocyte islets formation. FEBS Lett 2004; 576(1–2): 127–132.
36. Kocks C, Cho JH, Nehme N, Ulvila J, Pearson AM, et al. Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in drosophila. Cell 2005; 123(2): 335–346. 16239149
37. Bretscher AJ, Honti V, Binggeli O, Burri O, Poidevin M, et al. The nimrod transmembrane receptor eater is required for hemocyte attachment to the sessile compartment in drosophila melanogaster. Biol Open 2015.
38. Braun A, Hoffmann JA, Meister M. Analysis of the drosophila host defense in domino mutant larvae, which are devoid of hemocytes. Proc Natl Acad Sci U S A 1998; 95(24): 14337–14342. 9826701
39. Basset A, Khush RS, Braun A, Gardan L, Boccard F, et al. The phytopathogenic bacteria erwinia carotovora infects drosophila and activates an immune response. Proc Natl Acad Sci U S A 2000; 97(7): 3376–3381. 10725405
40. Brennan CA, Delaney JR, Schneider DS, Anderson KV. Psidin is required in drosophila blood cells for both phagocytic degradation and immune activation of the fat body. Curr Biol 2007; 17(1): 67–72. 17208189
41. Agaisse H, Petersen UM, Boutros M, Mathey-Prevot B, Perrimon N. Signaling role of hemocytes in drosophila JAK/STAT-dependent response to septic injury. Dev Cell 2003; 5(3): 441–450. 12967563
42. Shia AK, Glittenberg M, Thompson G, Weber AN, Reichhart JM, et al. Toll-dependent antimicrobial responses in drosophila larval fat body require spatzle secreted by haemocytes. J Cell Sci 2009; 122(Pt 24): 4505–4515. doi: 10.1242/jcs.049155 19934223
43. Foley E, O'Farrell PH. Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in drosophila. Genes Dev 2003; 17(1): 115–125. 12514104
44. Dijkers PF, O'Farrell PH. Drosophila calcineurin promotes induction of innate immune responses. Curr Biol 2007; 17(23): 2087–2093. 18060786
45. Charroux B, Royet J. Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the drosophila immune response. Proc Natl Acad Sci U S A 2009; 106(24): 9797–9802. doi: 10.1073/pnas.0903971106 19482944
46. Defaye A, Evans I, Crozatier M, Wood W, Lemaitre B, et al. Genetic ablation of drosophila phagocytes reveals their contribution to both development and resistance to bacterial infection. J Innate Immun 2009; 1(4): 322–334. doi: 10.1159/000210264 20375589
47. Parisi F, Stefanatos RK, Strathdee K, Yu Y, Vidal M. Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of toll and eiger/TNF signaling. Cell Rep 2014; 6(5): 855–867. doi: 10.1016/j.celrep.2014.01.039 24582964
48. Schmid MR, Anderl I, Vesala L, Vanha-aho LM, Deng XJ, et al. Control of drosophila blood cell activation via toll signaling in the fat body. PLoS One 2014; 9(8): e102568. doi: 10.1371/journal.pone.0102568 25102059
49. Hepburn L, Prajsnar TK, Klapholz C, Moreno P, Loynes CA, et al. Innate immunity. A spaetzle-like role for nerve growth factor beta in vertebrate immunity to staphylococcus aureus. Science 2014; 346(6209): 641–646. doi: 10.1126/science.1258705 25359976
50. Davis JM, Clay H, Lewis JL, Ghori N, Herbomel P, et al. Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity 2002; 17(6): 693–702. 12479816
51. Parikka M, Hammaren MM, Harjula SK, Halfpenny NJ, Oksanen KE, et al. Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish. PLoS Pathog 2012; 8(9): e1002944. doi: 10.1371/journal.ppat.1002944 23028333
52. Mielke ME, Peters C, Hahn H. Cytokines in the induction and expression of T-cell-mediated granuloma formation and protection in the murine model of listeriosis. Immunol Rev 1997; 158 : 79–93. 9314076
53. Sorrentino RP, Tokusumi T, Schulz RA. The friend of GATA protein U-shaped functions as a hematopoietic tumor suppressor in drosophila. Dev Biol 2007; 311(2): 311–323. 17936744
54. Tokusumi T, Sorrentino RP, Russell M, Ferrarese R, Govind S, et al. Characterization of a lamellocyte transcriptional enhancer located within the misshapen gene of drosophila melanogaster. PLoS One 2009; 4(7): e6429. doi: 10.1371/journal.pone.0006429 19641625
55. Kurucz E, Márkus R, Zsamboki J, Folkl-Medzihradszky K, Darula Z, et al. Nimrod, a putative phagocytosis receptor with EGF repeats in drosophila plasmatocytes. Curr Biol 2007; 17(7): 649–654. 17363253
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
