Skip to main content
Log in

A directed miniscreen for genes involved in the Drosophila anti-parasitoid immune response

  • Brief Communication
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Drosophila larvae react against eggs from the endoparasitoid wasp Leptopilina boulardi by surrounding them in a multilayered cellular capsule. Once a wasp egg is recognized as foreign, circulating macrophage-like cells, known as plasmatocytes, adhere to the invader. After spreading around the wasp egg, plasmatocytes form cellular junctions between the cells, effectively separating the egg from the hemocoel. Next, a second sub-type of circulating immunosurveillance cell (hemocyte), known as lamellocytes, adhere to either the wasp egg or more likely the plasmatocytes surrounding the egg. From these events, it is obvious that adhesion and cell shape change are an essential part of Drosophila's cellular immune response against parasitoid wasp eggs. To date, very few genes have been described as being necessary for a proper anti-parasitization response in Drosophila. With this in mind, we performed a directed genetic miniscreen to discover new genes required for this response. Many of the genes with an encapsulation defect have mammalian homologues involved in cellular adhesion, wound healing, and thrombosis, including extracellular matrix proteins, cellular adhesion molecules, and small GTPases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

References

  • Bidla G, Dushay MS, Theopold U (2007) Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog eiger. J Cell Sci 120:1209–1215

    Article  PubMed  CAS  Google Scholar 

  • Brehélin M (1982) Comparative study of structure and function of blood cells from two Drosophila species. Cell Tissue Res 221:607–615

    Article  PubMed  Google Scholar 

  • Burridge K, Wennerberg K (2004) Rho and rac take center stage. Cell 116:167–179

    Article  PubMed  CAS  Google Scholar 

  • Cichowski K, Brugge JS, Brass LF (1996) Thrombin receptor activation and integrin engagement stimulate tyrosine phosphorylation of the proto-oncogene product, p95vav, in platelets. J Biol Chem 271:7544–7550

    Article  PubMed  CAS  Google Scholar 

  • Gao G, Chen L, Dong B, Gu H, Dong H et al (2009) RhoA effector mDia1 is required for PI 3-kinase-dependent actin remodeling and spreading by thrombin in platelets. Biochem Biophys Res Commun 385:439–444

    Article  PubMed  CAS  Google Scholar 

  • Geberhiwot T, Ingerpuu S, Pedraza C, Neira M, Lehto U et al (1999) Blood platelets contain and secrete laminin-8 (alpha4beta1gamma1) and adhere to laminin-8 via alpha6beta1 integrin. Exp Cell Res 253:723–732

    Article  PubMed  CAS  Google Scholar 

  • Goto A, Kadowaki T, Kitagawa Y (2003) Drosophila Hemolectin gene is expressed in embryonic and larval hemocytes and its knock down causes bleeding defects. Dev Biol 264:582–591

    Article  PubMed  CAS  Google Scholar 

  • Heasman SJ, Ridley AJ (2008) Mammalian rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9:690–701

    Article  PubMed  CAS  Google Scholar 

  • Hime G, Saint R (1992) Zygotic expression of the pebble locus is required for cytokinesis during the postblastoderm mitoses of Drosophila. Development 114:165–171

    PubMed  CAS  Google Scholar 

  • Honti V, Kurucz E, Csordás G, Laurinyecz B, Márkus R, Andó I (2009) In vivo detection of lamellocytes in Drosophila melanogaster. Immunol Lett 126:83–84

    Article  PubMed  CAS  Google Scholar 

  • Irving P, Ubeda J, Doucet D, Troxler L, Lagueux M et al (2005) New insights into Drosophila larval hemocyte functions through genome-wide analysis. Cell Microbiol 7:335–350

    Article  PubMed  CAS  Google Scholar 

  • Kim SH, Turnbull J, Guimond S (2011) Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol 209:139–151

    Article  PubMed  CAS  Google Scholar 

  • Kurucz E, Zettervall CJ, Sinka R, Vilmos P, Pivarcsi A et al (2003) Hemese, a hemocyte-specific transmembrane protein, affects the cellular immune response in Drosophila. Proc Natl Acad Sci USA 100:2622–2627

    Article  PubMed  CAS  Google Scholar 

  • Kurucz E, Markus R, Zsamboki J, Folkl-Medzihradszky K, Darula Z et al (2007) Nimrod, a putative phagocytosis receptor with EGF repeats in Drosophila plasmatocytes. Curr Biol 17:649–654

    Article  PubMed  CAS  Google Scholar 

  • Lanot R, Zachary D, Holder F, Meister M (2001) Postembryonic hematopoiesis in Drosophila. Dev Biol 230:243–257

    Article  PubMed  CAS  Google Scholar 

  • Lavine MD, Strand MR (2003) Haemocytes from Pseudoplusia includens express multiple α and β integrin subunits. Insect Mol Biol 12:441–452

    Article  PubMed  CAS  Google Scholar 

  • Lemaitre B, Hoffmann J (2007) The host defense of Drosophila melanogaster. Annu Rev Immunol 25:697–743

    Article  PubMed  CAS  Google Scholar 

  • Markus R, Laurinyecz B, Kurucz E, Honti V, Bajusz I et al (2009) Sessile hemocytes as a hematopoietic compartment in Drosophila melanogaster. Proc Natl Acad Sci USA 106:4805–4809

    Article  PubMed  CAS  Google Scholar 

  • Meister M, Richards G (1996) Ecdysone and insect immunity: the maturation of the inducibility of the diptericin gene in Drosophila larvae. Insect Biochem Mol Biol 26:155–160

    Article  PubMed  CAS  Google Scholar 

  • Miyakawa Y, Oda A, Druker BJ, Ozaki K, Handa M et al (1997) Thrombopoietin and thrombin induce tyrosine phosphorylation of vav in human blood platelets. Blood 89:2789–2798

    PubMed  CAS  Google Scholar 

  • O'Keefe L, Somers W, Harley A, Saint R (2001) The pebble GTP exchange factor and the control of cytokinesis. Cell Struct Funct 26:619–626

    Article  PubMed  Google Scholar 

  • Pandey D, Goyal P, Dwivedi S, Siess W (2009) Unraveling a novel Rac1-mediated signaling pathway that regulates cofilin dephosphorylation and secretion in thrombin-stimulated platelets. Blood 114:415–424

    Article  PubMed  CAS  Google Scholar 

  • Pleines I, Elvers M, Strehl A, Pozgajova M, Varga-Szabo D et al (2009) Rac1 is essential for phospholipase C-gamma2 activation in platelets. Pflugers Arch 457:1173–1185

    Article  PubMed  CAS  Google Scholar 

  • Pleines I, Eckly A, Elvers M, Hagedorn I, Eliautou S et al (2010) Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood 115:3364–3373

    Article  PubMed  CAS  Google Scholar 

  • Prevost N, Woulfe D, Tanaka T, Brass LF (2002) Interactions between eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc Natl Acad Sci USA 99:9219–9224

    Article  PubMed  CAS  Google Scholar 

  • Prevost N, Woulfe DS, Tognolini M, Tanaka T, Jian W et al (2004) Signaling by ephrinB1 and eph kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1. Blood 103:1348–1355

    Article  PubMed  CAS  Google Scholar 

  • Prevost N, Woulfe DS, Jiang H, Stalker TJ, Marchese P et al (2005) Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci USA 102:9820–9825

    Article  PubMed  CAS  Google Scholar 

  • Prokopenko SN, Brumby A, O'Keefe L, Prior L, He Y, Saint R, Bellen HJ (1999) A putative exchange factor for Rho1 GTPase is required for initiation of cytokinesis in Drosophila. Genes Dev 13:2301–2314

    Article  PubMed  CAS  Google Scholar 

  • Raftopoulou M, Hall A (2004) Cell migration: rho GTPases lead the way. Dev Biol 265:23–32

    Article  PubMed  CAS  Google Scholar 

  • Ridley AJ (2001) Rho GTPases and cell migration. J Cell Sci 114:2713–2722

    PubMed  CAS  Google Scholar 

  • Ridley AJ (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 16:522–529

    Article  PubMed  CAS  Google Scholar 

  • Rizki RM, Rizki TM (1979) Cell interactions in the differentiation of a melanotic tumor in Drosophila. Differentiation 12:167–178

    Article  PubMed  CAS  Google Scholar 

  • Rizki TM, Rizki RM (1992) Lamellocyte differentiation in Drosophila larvae parasitized by Leptopilina. Dev Comp Immunol 16:103–110

    Article  PubMed  CAS  Google Scholar 

  • Russo J, Dupas S, Frey F, Carton Y, Brehelin M (1996) Insect immunity: early events in the encapsulation process of parasitoid (Leptopilina boulardi) eggs in resistant and susceptible strains of Drosophila. Parasitology 112:135–142

    Article  PubMed  Google Scholar 

  • Sorrentino RP, Carton Y, Govind S (2002) Cellular immune response to parasite infection in the Drosophila lymph gland is developmentally regulated. Dev Biol 243:65–80

    Article  PubMed  CAS  Google Scholar 

  • Sorrentino RP, Melk JP, Govind S (2004) Genetic analysis of contributions of dorsal group and JAK–Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila. Genetics 166:1343–1356

    Article  PubMed  CAS  Google Scholar 

  • Tatsumoto T, Xie X, Blumenthal R, Okamoto I, Miki T (1999) Human ECT2 is an exchange factor for rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis. J Cell Biol 147:921–928

    Article  PubMed  CAS  Google Scholar 

  • Vega FM, Ridley AJ (2008) Rho GTPases in cancer cell biology. FEBS Lett 582:2093–2101

    Article  PubMed  CAS  Google Scholar 

  • Williams MJ (2007) Drosophila hemopoiesis and cellular immunity. J Immunol 178:4711–4716

    PubMed  CAS  Google Scholar 

  • Williams MJ (2009) The Drosophila cell adhesion molecule neuroglian regulates lissencephaly-1 localization in circulating immunosurveillance cells. BMC Immunol 10:17

    Article  PubMed  Google Scholar 

  • Williams MJ, Ando I, Hultmark D (2005) Drosophila melanogaster Rac2 is necessary for a proper cellular immune response. Genes Cells 10:813–823

    Article  PubMed  CAS  Google Scholar 

  • Williams MJ, Wiklund M, Wikman S, Hultmark D (2006) Rac1 signalling in the Drosophila larval cellular immune response. J Cell Sci 119:2015–2024

    Article  PubMed  CAS  Google Scholar 

  • Xavier MJ, Williams MJ (2011) The Rho-family GTPase Rac1 regulates integrin localization in Drosophila immunosurveillance cells. PLoS One 6:e19504

    Article  PubMed  CAS  Google Scholar 

  • Zettervall C, Anderl I, Williams MJ, Palmer R, Kurucz E et al (2004) A directed miniscreen for genes involved in Drosophila blood cell activation. Proc Natl Acad Sci USA 101:14192–14197

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. John B. Thomas (The Salk Institute) for his generous gift of the Eph x652 flies. This work was partially supported by funds from the BBSRC, the Royal Society, the Wellcome Trust, the University of Aberdeen, and the University of Edinburgh.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael J. Williams.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Howell, L., Sampson, C.J., Xavier, M.J. et al. A directed miniscreen for genes involved in the Drosophila anti-parasitoid immune response. Immunogenetics 64, 155–161 (2012). https://doi.org/10.1007/s00251-011-0571-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-011-0571-3

Keywords

Navigation