Chapter 5 : Advances in Myeloid-Like Cell Origins and Functions in the Model Organism

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Innate immunity shields all metazoans against infections. Its main features, including sensing, signaling, and effector mechanisms, are conserved from invertebrates to vertebrates. The hallmark of innate immunity is its reliance on a limited set of non-clonally-distributed receptors, which detect signature molecules of microbial origin and activate subsequent effector mechanisms. This concept, coined by Charles Janeway in 1989 as the self-versus-microbial-nonself discrimination system, has opened a large field of research for the so-called pattern recognition receptors (PRRs) and their cognate microbial elicitors, the pathogen-associated molecular patterns ( ). has rapidly emerged as a particularly suitable model organism for this research. Indeed, like all invertebrates, exclusively relies on an innate immune system, which fends off infections in highly contaminated environments. Most importantly, has benefited from more than a century of laboratory-use experience, yielding a wide array of molecular and genetic tools. Investigations on the defense reactions in flies rapidly provided valuable insights into the evolutionary conservation between insects and mammals, including humans, of the signal transduction pathways that control the innate immune system ( ). Most prominent is the seminal finding in 1996 of the chief role of the Toll signaling pathway in the control of fungal infections in ( ). This study paved the way for the identification of the first mammalian PRR, Toll-like receptor 4 (the launching member of the TLR family), and the understanding of the innate immune system’s molecular mechanisms for sensing, signaling, and activation of adaptive immunity ( ). Following more than 2 decades of in-depth analysis exploiting several infection models combined with genetic and genomic approaches, research on the immune system revealed complex interconnected humoral and cellular processes, both of which show striking similarities with those of mammals. In this review, we provide a global view of the host defense while drawing particular attention to the role of its monocyte-macrophage-like cells, the plasmatocytes. We provide general insights on the recent advances in hematopoiesis and give a comprehensive summary on the so-far identified receptors involved in microbial detection, binding, and the ensuing internalization processes.

Citation: El Chamy L, Matt N, Reichhart J. 2017. Advances in Myeloid-Like Cell Origins and Functions in the Model Organism , p 59-77. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0038-2016
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Figure 1

immune reactions. immune response comprises a local barrier response based on the secretion of AMPs and a fine-tuned oxidative response. Breaching of this barrier triggers a systemic humoral antimicrobial response as well as a cellular response (refer to text for a detailed description).

Citation: El Chamy L, Matt N, Reichhart J. 2017. Advances in Myeloid-Like Cell Origins and Functions in the Model Organism , p 59-77. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0038-2016
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Figure 2

hematopoiesis. Hematopoiesis in starts during embryogenesis and continues till the adult stage. (a) Embryonic hematopoiesis. Schematic presentations of stage 10 and 16 embryos with the head on the left and the ventral axis facing down. The gut is shown in dashed lines (dv, dorsal vessel; e, esophagus; pv, proventriculus; mg, midgut; hg, hindgut). embryonic hemocyte progenitors, the prohemocytes, emanate from the procephalic mesoderm. After their differentiation, plasmatocytes (shown in blue) migrate to populate the whole embryo, whereas crystal cells (shown in yellow) remain around their points of origin and populate the proventriculus. (b) Larval hematopoiesis. Schematic presentation of a third instar larva with the head at left and the ventral axis facing down (top). In the larvae, embryonic hemocytes proliferate within the hematopoietic pockets (HPs), giving rise to sessile hemocytes, which could differentiate into plasmatocytes but also crystal cells and lamellocytes in the case of parasitization. In the larvae, another center of hematopoiesis, the lymph gland (LG), originates from an anlage of the thoracic mesoderm and differentiates into four (to six) bilaterally paired lobes along the anterior part of the dorsal vessel. The cellular organization of the LG is shown (bottom). The primary lobes are indicated in red, the posterior signaling center (PSC) in purple, and the posterior lobes in blue. Within the primary lobes, core progenitor hemocytes are shown in purple, progenitors in dark blue, and plasmatocytes and crystal cells in light blue and yellow, respectively. LG-derived hemocytes are normally released at the beginning of pupariation only under immune challenge. A detailed description of signaling pathways controlling hematopoiesis is reviewed in reference . (c) Adult hematopoiesis. Four hematopoietic hubs (HH) have been identified in the dorsal part of adult fly abdomen. These hubs enclose hematopoietic progenitors, derived from the third and fourth lobes of the LG, together with differentiated hemocytes of embryonic and larval origins.

Citation: El Chamy L, Matt N, Reichhart J. 2017. Advances in Myeloid-Like Cell Origins and Functions in the Model Organism , p 59-77. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0038-2016
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1. Janeway CA Jr . 1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54( Pt 1) : 1 13.
2. Ferrandon D,, Imler JL,, Hetru C,, Hoffmann JA . 2007. The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 7 : 862 874.
3. Lemaitre B,, Nicolas E,, Michaut L,, Reichhart JM,, Hoffmann JA . 1996. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86 : 973 983.
4. Medzhitov R,, Preston-Hurlburt P,, Janeway CA Jr . 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388 : 394 397.
5. Poltorak A,, He X,, Smirnova I,, Liu MY,, Van Huffel C,, Du X,, Birdwell D,, Alejos E,, Silva M,, Galanos C,, Freudenberg M,, Ricciardi-Castagnoli P,, Layton B,, Beutler B . 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282 : 2085 2088.
6. Kawai T,, Akira S . 2011. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34 : 637 650.
7. Ferrandon D . 2013. The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience. Curr Opin Immunol 25 : 59 70.
8. El Chamy L,, Matt N,, Ntwasa M,, Reichhart JM . 2015. The multilayered innate immune defense of the gut. Biomed J 38 : 276 284.
9. Lemaitre B,, Hoffmann J . 2007. The host defense of Drosophila melanogaster . Annu Rev Immunol 25 : 697 743.
10. Valanne S,, Wang JH,, Rämet M . 2011. The Drosophila Toll signaling pathway. J Immunol 186 : 649 656.
11. Myllymäki H,, Valanne S,, Rämet M . 2014. The Drosophila Imd signaling pathway. J Immunol 192 : 3455 3462.
12. Royet J,, Reichhart JM,, Hoffmann JA . 2005. Sensing and signaling during infection in Drosophila . Curr Opin Immunol 17 : 11 17.
13. Charroux B,, Rival T,, Narbonne-Reveau K,, Royet J . 2009. Bacterial detection by Drosophila peptidoglycan recognition proteins. Microbes Infect 11 : 631 636.
14. Jang IH,, Chosa N,, Kim SH,, Nam HJ,, Lemaitre B,, Ochiai M,, Kambris Z,, Brun S,, Hashimoto C,, Ashida M,, Brey PT,, Lee WJ . 2006. A Spätzle-processing enzyme required for Toll signaling activation in Drosophila innate immunity. Dev Cell 10 : 45 55.
15. El Chamy L,, Leclerc V,, Caldelari I,, Reichhart JM . 2008. Sensing of ‘danger signals’ and pathogen-associated molecular patterns defines binary signaling pathways ‘upstream’ of Toll. Nat Immunol 9 : 1165 1170.
16. Gottar M,, Gobert V,, Matskevich AA,, Reichhart JM,, Wang C,, Butt TM,, Belvin M,, Hoffmann JA,, Ferrandon D . 2006. Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell 127 : 1425 1437.
17. Cerenius L,, Kawabata S,, Lee BL,, Nonaka M,, Soderhall K . 2010. Proteolytic cascades and their involvement in invertebrate immunity. Trends Biochem Sci 35 : 575 583.
18. Tang H . 2009. Regulation and function of the melanization reaction in Drosophila . Fly (Austin) 3 : 105 111.
19. Tang H,, Kambris Z,, Lemaitre B,, Hashimoto C . 2008. A serpin that regulates immune melanization in the respiratory system of Drosophila . Dev Cell 15 : 617 626.
20. Boutros M,, Agaisse H,, Perrimon N . 2002. Sequential activation of signaling pathways during innate immune responses in Drosophila . Dev Cell 3 : 711 722.
21. Rämet M,, Lanot R,, Zachary D,, Manfruelli P . 2002. JNK signaling pathway is required for efficient wound healing in Drosophila . Dev Biol 241 : 145 156.
22. Galko MJ,, Krasnow MA . 2004. Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biol 2 : E239. doi:10.1371/journal.pbio.0020239.
23. Lesch C,, Jo J,, Wu Y,, Fish GS,, Galko MJ . 2010. A targeted UAS-RNAi screen in Drosophila larvae identifies wound closure genes regulating distinct cellular processes. Genetics 186 : 943 957.
24. Kwon YC,, Baek SH,, Lee H,, Choe KM . 2010. Nonmuscle myosin II localization is regulated by JNK during Drosophila larval wound healing. Biochem Biophys Res Commun 393 : 656 661.
25. Ekengren S,, Hultmark D . 2001. A family of Turandot-related genes in the humoral stress response of Drosophila . Biochem Biophys Res Commun 284 : 998 1003.
26. Agaisse H,, Petersen UM,, Boutros M,, Mathey-Prevot B,, Perrimon N . 2003. Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury. Dev Cell 5 : 441 450.
27. Brun S,, Vidal S,, Spellman P,, Takahashi K,, Tricoire H,, Lemaitre B . 2006. The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila . Genes Cells 11 : 397 407.
28. Woodcock KJ,, Kierdorf K,, Pouchelon CA,, Vivancos V,, Dionne MS,, Geissmann F . 2015. Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet. Immunity 42 : 133 144.
29. Chakrabarti S,, Dudzic JP,, Li X,, Collas EJ,, Boquete JP,, Lemaitre B . 2016. Remote control of intestinal stem cell activity by haemocytes in Drosophila . PLoS Genet 12 : e1006089. doi:10.1371/journal.pgen.1006089.
30. Martins N,, Imler JL,, Meignin C . 2016. Discovery of novel targets for antivirals: learning from flies. Curr Opin Virol 20 : 64 70.
31. Xu J,, Cherry S . 2014. Viruses and antiviral immunity in Drosophila . Dev Comp Immunol 42 : 67 84.
32. Dostert C,, Jouanguy E,, Irving P,, Troxler L,, Galiana-Arnoux D,, Hetru C,, Hoffmann JA,, Imler JL . 2005. The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila. Nat Immunol 6 : 946 953.
33. Carpenter J,, Hutter S,, Baines JF,, Roller J,, Saminadin-Peter SS,, Parsch J,, Jiggins FM . 2009. The transcriptional response of Drosophila melanogaster to infection with the sigma virus (Rhabdoviridae). PLoS One 4 : e6838. doi:10.1371/journal.pone.0006838.
34. Castorena KM,, Stapleford KA,, Miller DJ . 2010. Complementary transcriptomic, lipidomic, and targeted functional genetic analyses in cultured Drosophila cells highlight the role of glycerophospholipid metabolism in Flock House virus RNA replication. BMC Genomics 11 : 183. doi:10.1186/1471-2164-11-183.
35. Mudiganti U,, Hernandez R,, Brown DT . 2010. Insect response to alphavirus infection—establishment of alphavirus persistence in insect cells involves inhibition of viral polyprotein cleavage. Virus Res 150 : 73 84.
36. Xu J,, Grant G,, Sabin LR,, Gordesky-Gold B,, Yasunaga A,, Tudor M,, Cherry S . 2012. Transcriptional pausing controls a rapid antiviral innate immune response in Drosophila . Cell Host Microbe 12 : 531 543.
37. Kemp C,, Mueller S,, Goto A,, Barbier V,, Paro S,, Bonnay F,, Dostert C,, Troxler L,, Hetru C,, Meignin C,, Pfeffer S,, Hoffmann JA,, Imler JL . 2013. Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila . J Immunol 190 : 650 658.
38. Cordes EJ,, Licking-Murray KD,, Carlson KA . 2013. Differential gene expression related to Nora virus infection of Drosophila melanogaster . Virus Res 175 : 95 100.
39. Huang Z,, Kingsolver MB,, Avadhanula V,, Hardy RW . 2013. An antiviral role for antimicrobial peptides during the arthropod response to alphavirus replication. J Virol 87 : 4272 4280.
40. Lamiable O,, Imler JL . 2014. Induced antiviral innate immunity in Drosophila . Curr Opin Microbiol 20 : 62 68.
41. Zambon RA,, Nandakumar M,, Vakharia VN,, Wu LP . 2005. The Toll pathway is important for an antiviral response in Drosophila . Proc Natl Acad Sci U S A 102 : 7257 7262.
42. Avadhanula V,, Weasner BP,, Hardy GG,, Kumar JP,, Hardy RW . 2009. A novel system for the launch of alphavirus RNA synthesis reveals a role for the Imd pathway in arthropod antiviral response. PLoS Pathog 5 : e1000582. doi:10.1371/journal.ppat.1000582.
43. Costa A,, Jan E,, Sarnow P,, Schneider D . 2009. The Imd pathway is involved in antiviral immune responses in Drosophila . PLoS One 4 : e7436. doi:10.1371/journal.pone.0007436.
44. Rancès E,, Johnson TK,, Popovici J,, Iturbe-Ormaetxe I,, Zakir T,, Warr CG,, O’Neill SL . 2013. The Toll and Imd pathways are not required for Wolbachia-mediated dengue virus interference. J Virol 87 : 11945 11949.
45. Ferreira AG,, Naylor H,, Esteves SS,, Pais IS,, Martins NE,, Teixeira L . 2014. The Toll-dorsal pathway is required for resistance to viral oral infection in Drosophila . PLoS Pathog 10 : e1004507. doi:10.1371/journal.ppat.1004507.
46. Merkling SH,, Bronkhorst AW,, Kramer JM,, Overheul GJ,, Schenck A,, Van Rij RP . 2015. The epigenetic regulator G9a mediates tolerance to RNA virus infection in Drosophila . PLoS Pathog 11 : e1004692. doi:10.1371/journal.ppat.1004692.
47. Shelly S,, Lukinova N,, Bambina S,, Berman A,, Cherry S . 2009. Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus. Immunity 30 : 588 598.
48. Liu B,, Behura SK,, Clem RJ,, Schneemann A,, Becnel J,, Severson DW,, Zhou L . 2013. P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster . PLoS Pathog 9 : e1003137. doi:10.1371/journal.ppat.1003137.
49. Nainu F,, Tanaka Y,, Shiratsuchi A,, Nakanishi Y . 2015. Protection of insects against viral infection by apoptosis-dependent phagocytosis. J Immunol 195 : 5696 5706.
50. Galiana-Arnoux D,, Dostert C,, Schneemann A,, Hoffmann JA,, Imler JL . 2006. Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat Immunol 7 : 590 597.
51. van Rij RP,, Saleh MC,, Berry B,, Foo C,, Houk A,, Antoniewski C,, Andino R . 2006. The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster . Genes Dev 20 : 2985 2995.
52. Wang XH,, Aliyari R,, Li WX,, Li HW,, Kim K,, Carthew R,, Atkinson P,, Ding SW . 2006. RNA interference directs innate immunity against viruses in adult Drosophila . Science 312 : 452 454.
53. Mueller S,, Gausson V,, Vodovar N,, Deddouche S,, Troxler L,, Perot J,, Pfeffer S,, Hoffmann JA,, Saleh MC,, Imler JL . 2010. RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila . Proc Natl Acad Sci U S A 107 : 19390 19395.
54. Bronkhorst AW,, van Cleef KW,, Vodovar N,, Ince IA,, Blanc H,, Vlak JM,, Saleh MC,, van Rij RP . 2012. The DNA virus Invertebrate iridescent virus 6 is a target of the Drosophila RNAi machinery. Proc Natl Acad Sci U S A 109 : E3604 E3613. doi:10.1073/pnas.1207213109.
55. Bernstein E,, Caudy AA,, Hammond SM,, Hannon GJ . 2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409 : 363 366.
56. Rand TA,, Ginalski K,, Grishin NV,, Wang X . 2004. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. Proc Natl Acad Sci U S A 101 : 14385 14389.
57. Okamura K,, Ishizuka A,, Siomi H,, Siomi MC . 2004. Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 18 : 1655 1666.
58. Deddouche S,, Matt N,, Budd A,, Mueller S,, Kemp C,, Galiana-Arnoux D,, Dostert C,, Antoniewski C,, Hoffmann JA,, Imler JL . 2008. The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila. Nat Immunol 9 : 1425 1432.
59. Desmet CJ,, Ishii KJ . 2012. Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12 : 479 491.
60. Meister M . 2004. Blood cells of Drosophila: cell lineages and role in host defence. Curr Opin Immunol 16 : 10 15.
61. Crozatier M,, Meister M . 2007. Drosophila haematopoiesis. Cell Microbiol 9 : 1117 1126.
62. Letourneau M,, Lapraz F,, Sharma A,, Vanzo N,, Waltzer L,, Crozatier M . 2016. Drosophila hematopoiesis under normal conditions and in response to immune stress. FEBS Lett 590 : 4034 4051.
63. Gold KS,, Bruckner K . 2014. Drosophila as a model for the two myeloid blood cell systems in vertebrates. Exp Hematol 42 : 717 727.
64. Holz A,, Bossinger B,, Strasser T,, Janning W,, Klapper R . 2003. The two origins of hemocytes in Drosophila . Development 130 : 4955 4962.
65. Tepass U,, Fessler LI,, Aziz A,, Hartenstein V . 1994. Embryonic origin of hemocytes and their relationship to cell death in Drosophila . Development 120 : 1829 1837.
66. Franc NC,, Heitzler P,, Ezekowitz RA,, White K . 1999. Requirement for Croquemort in phagocytosis of apoptotic cells in Drosophila . Science 284 : 1991 1994.
67. Franc NC . 2002. Phagocytosis of apoptotic cells in mammals, Caenorhabditis elegans and Drosophila melanogaster: molecular mechanisms and physiological consequences. Front Biosci 7 : d1298 d1313.
68. Sears HC,, Kennedy CJ,, Garrity PA . 2003. Macrophage-mediated corpse engulfment is required for normal Drosophila CNS morphogenesis. Development 130 : 3557 3565.
69. Olofsson B,, Page DT . 2005. Condensation of the central nervous system in embryonic Drosophila is inhibited by blocking hemocyte migration or neural activity. Dev Biol 279 : 233 243.
70. Defaye A,, Evans I,, Crozatier M,, Wood W,, Lemaitre B,, Leulier F . 2009. Genetic ablation of Drosophila phagocytes reveals their contribution to both development and resistance to bacterial infection. J Innate Immun 1 : 322 334.
71. Wood W,, Jacinto A . 2007. Drosophila melanogaster embryonic haemocytes: masters of multitasking. Nat Rev Mol Cell Biol 8 : 542 551.
72. Terriente-Felix A,, Li J,, Collins S,, Mulligan A,, Reekie I,, Bernard F,, Krejci A,, Bray S . 2013. Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme. Development 140 : 926 937.
73. Lebestky T,, Chang T,, Hartenstein V,, Banerjee U . 2000. Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288 : 146 149.
74. Bernardoni R,, Vivancos V,, Giangrande A . 1997. glide/gcm is expressed and required in the scavenger cell lineage. Dev Biol 191 : 118 130.
75. Lebestky T,, Jung SH,, Banerjee U . 2003. A Serrate-expressing signaling center controls Drosophila hematopoiesis. Genes Dev 17 : 348 353.
76. Muratoglu S,, Garratt B,, Hyman K,, Gajewski K,, Schulz RA,, Fossett N . 2006. Regulation of Drosophila Friend of GATA gene, u-shaped, during hematopoiesis: a direct role for Serpent and Lozenge. Dev Biol 296 : 561 579.
77. Bataille L,, Auge B,, Ferjoux G,, Haenlin M,, Waltzer L . 2005. Resolving embryonic blood cell fate choice in Drosophila: interplay of GCM and RUNX factors. Development 132 : 4635 4644.
78. Evans CJ,, Hartenstein V,, Banerjee U . 2003. Thicker than blood: conserved mechanisms in Drosophila and vertebrate hematopoiesis. Dev Cell 5 : 673 690.
79. Markus R,, Laurinyecz B,, Kurucz E,, Honti V,, Bajusz I,, Sipos B,, Somogyi K,, Kronhamn J,, Hultmark D,, Ando I . 2009. Sessile hemocytes as a hematopoietic compartment in Drosophila melanogaster . Proc Natl Acad Sci U S A 106 : 4805 4809.
80. Zaidman-Remy A,, Regan JC,, Brandao AS,, Jacinto A . 2012. The Drosophila larva as a tool to study gut-associated macrophages: PI3K regulates a discrete hemocyte population at the proventriculus. Dev Comp Immunol 36 : 638 647.
81. Stofanko M,, Kwon SY,, Badenhorst P . 2008. A misexpression screen to identify regulators of Drosophila larval hemocyte development. Genetics 180 : 253 267.
82. Hashimoto D,, Chow A,, Noizat C,, Teo P,, Beasley MB,, Leboeuf M,, Becker CD,, See P,, Price J,, Lucas D,, Greter M,, Mortha A,, Boyer SW,, Forsberg EC,, Tanaka M,, van Rooijen N,, Garcia-Sastre A,, Stanley ER,, Ginhoux F,, Frenette PS,, Merad M . 2013. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38 : 792 804.
83. Makhijani K,, Alexander B,, Tanaka T,, Rulifson E,, Bruckner K . 2011. The peripheral nervous system supports blood cell homing and survival in the Drosophila larva. Development 138 : 5379 5391.
84. Makhijani K,, Bruckner K . 2012. Of blood cells and the nervous system: hematopoiesis in the Drosophila larva. Fly (Austin) 6 : 254 260.
85. Honti V,, Csordas G,, Markus R,, Kurucz E,, Jankovics F,, Ando I . 2010. Cell lineage tracing reveals the plasticity of the hemocyte lineages and of the hematopoietic compartments in Drosophila melanogaster . Mol Immunol 47 : 1997 2004.
86. Leitão AB,, Sucena E . 2015. Drosophila sessile hemocyte clusters are true hematopoietic tissues that regulate larval blood cell differentiation. eLife 4 : e06166. doi:10.7554/eLife.06166.
87. Lanot R,, Zachary D,, Holder F,, Meister M . 2001. Postembryonic hematopoiesis in Drosophila . Dev Biol 230 : 243 257.
88. Pastor-Pareja JC,, Wu M,, Xu T . 2008. An innate immune response of blood cells to tumors and tissue damage in Drosophila . Dis Model Mech 1 : 144 154; discussion 153.
89. Zettervall CJ,, Anderl I,, Williams MJ,, Palmer R,, Kurucz E,, Ando I,, Hultmark D . 2004. A directed screen for genes involved in Drosophila blood cell activation. Proc Natl Acad Sci U S A 101 : 14192 14197.
90. Babcock DT,, Brock AR,, Fish GS,, Wang Y,, Perrin L,, Krasnow MA,, Galko MJ . 2008. Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae. Proc Natl Acad Sci U S A 105 : 10017 10022.
91. Grigorian M,, Mandal L,, Hartenstein V . 2011. Hematopoiesis at the onset of metamorphosis: terminal differentiation and dissociation of the Drosophila lymph gland. Dev Genes Evol 221 : 121 131.
92. Rugendorff AE,, Younossi-Hartenstein A,, Hartenstein V . 1994. Embryonic origin and differentiation of the Drosophila heart. Roux’s Arch Dev Bio 203 : 266 280.
93. Mandal L,, Banerjee U,, Hartenstein V . 2004. Evidence for a fruit fly hemangioblast and similarities between lymph-gland hematopoiesis in fruit fly and mammal aorta-gonadal-mesonephros mesoderm. Nat Genet 36 : 1019 1023.
94. Hartenstein V . 2006. Blood cells and blood cell development in the animal kingdom. Annu Rev Cell Dev Biol 22 : 677 712.
95. Jung SH,, Evans CJ,, Uemura C,, Banerjee U . 2005. The Drosophila lymph gland as a developmental model of hematopoiesis. Development 132 : 2521 2533.
96. Krzemień J,, Dubois L,, Makki R,, Meister M,, Vincent A,, Crozatier M . 2007. Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre. Nature 446 : 325 328.
97. Mandal L,, Martinez-Agosto JA,, Evans CJ,, Hartenstein V,, Banerjee U . 2007. A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors. Nature 446 : 320 324.
98. Crozatier M,, Krzemień J,, Vincent A . 2007. The hematopoietic niche: a Drosophila model, at last. Cell Cycle 6 : 1443 1444.
99. Minakhina S,, Steward R . 2010. Hematopoietic stem cells in Drosophila . Development 137 : 27 31.
100. Mondal BC,, Mukherjee T,, Mandal L,, Evans CJ,, Sinenko SA,, Martinez-Agosto JA,, Banerjee U . 2011. Interaction between differentiating cell- and niche-derived signals in hematopoietic progenitor maintenance. Cell 147 : 1589 1600.
101. Benmimoun B,, Polesello C,, Haenlin M,, Waltzer L . 2015. The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche. Proc Natl Acad Sci U S A 112 : 9052 9057.
102. Morin-Poulard I,, Sharma A,, Louradour I,, Vanzo N,, Vincent A,, Crozatier M . 2016. Vascular control of the Drosophila haematopoietic microenvironment by Slit/Robo signalling. Nat Commun 7 : 11634. doi:10.1038/ncomms11634.
103. Sinenko SA,, Mandal L,, Martinez-Agosto JA,, Banerjee U . 2009. Dual role of Wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila . Dev Cell 16 : 756 763.
104. Shim J,, Mukherjee T,, Banerjee U . 2012. Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila . Nat Cell Biol 14 : 394 400.
105. Owusu-Ansah E,, Banerjee U . 2009. Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature 461 : 537 541.
106. Shim J,, Mukherjee T,, Mondal BC,, Liu T,, Young GC,, Wijewarnasuriya DP,, Banerjee U . 2013. Olfactory control of blood progenitor maintenance. Cell 155 : 1141 1153.
107. Oyallon J,, Vanzo N,, Krzemień J,, Morin-Poulard I,, Vincent A,, Crozatier M . 2016. Two independent functions of Collier/Early B Cell Factor in the control of Drosophila blood cell homeostasis. PLoS One 11 : e0148978. doi:10.1371/journal.pone.0148978.
108. Qiu P,, Pan PC,, Govind S . 1998. A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development 125 : 1909 1920.
109. Myrick KV,, Dearolf CR . 2000. Hyperactivation of the Drosophila Hop Jak kinase causes the preferential overexpression of eIF1A transcripts in larval blood cells. Gene 244 : 119 125.
110. Minakhina S,, Tan W,, Steward R . 2011. JAK/STAT and the GATA factor Pannier control hemocyte maturation and differentiation in Drosophila. Dev Biol 352 : 308 316.
111. Pennetier D,, Oyallon J,, Morin-Poulard I,, Dejean S,, Vincent A,, Crozatier M . 2012. Size control of the Drosophila hematopoietic niche by bone morphogenetic protein signaling reveals parallels with mammals. Proc Natl Acad Sci U S A 109 : 3389 3394.
112. Remillieux-Leschelle N,, Santamaria P,, Randsholt NB . 2002. Regulation of larval hematopoiesis in Drosophila melanogaster: a role for the multi sex combs gene. Genetics 162 : 1259 1274.
113. Minakhina S,, Druzhinina M,, Steward R . 2007. Zfrp8, the Drosophila ortholog of PDCD2, functions in lymph gland development and controls cell proliferation. Development 134 : 2387 2396.
114. Crozatier M,, Ubeda JM,, Vincent A,, Meister M . 2004. Cellular immune response to parasitization in Drosophila requires the EBF orthologue Collier. PLoS Biol 2 : E196. doi:10.1371/journal.pbio.0020196.
115. Rizki TM,, Rizki RM . 1992. Lamellocyte differentiation in Drosophila larvae parasitized by Leptopilina . Dev Comp Immunol 16 : 103 110.
116. Sinenko SA,, Shim J,, Banerjee U . 2012. Oxidative stress in the haematopoietic niche regulates the cellular immune response in Drosophila . EMBO Rep 13 : 83 89.
117. Ghosh S,, Singh A,, Mandal S,, Mandal L . 2015. Active hematopoietic hubs in Drosophila adults generate hemocytes and contribute to immune response. Dev Cell 33 : 478 488.
118. Martinek N,, Shahab J,, Saathoff M,, Ringuette M . 2008. Haemocyte-derived SPARC is required for collagen-IV-dependent stability of basal laminae in Drosophila embryos. J Cell Sci 121 : 1671 1680.
119. Bunt S,, Hooley C,, Hu N,, Scahill C,, Weavers H,, Skaer H . 2010. Hemocyte-secreted type IV collagen enhances BMP signaling to guide renal tubule morphogenesis in Drosophila . Dev Cell 19 : 296 306.
120. Fessler JH,, Fessler LI . 1989. Drosophila extracellular matrix. Annu Rev Cell Biol 5 : 309 339.
121. Gullberg D,, Fessler LI,, Fessler JH . 1994. Differentiation, extracellular matrix synthesis, and integrin assembly by Drosophila embryo cells cultured on vitronectin and laminin substrates. Dev Dyn 199 : 116 128.
122. Hortsch M,, Olson A,, Fishman S,, Soneral SN,, Marikar Y,, Dong R,, Jacobs JR . 1998. The expression of MDP-1, a component of Drosophila embryonic basement membranes, is modulated by apoptotic cell death. Int J Dev Biol 42 : 33 42.
123. Lamiable O,, Arnold J,, de Faria IJ,, Olmo RP,, Bergami F,, Meignin C,, Hoffmann JA,, Marques JT,, Imler JL . 2016. Analysis of the contribution of hemocytes and autophagy to Drosophila antiviral immunity. J Virol 90 : 5415 5426.
124. Vlisidou I,, Wood W . 2015. Drosophila blood cells and their role in immune responses. FEBS J 282 : 1368 1382.
125. Elrod-Erickson M,, Mishra S,, Schneider D . 2000. Interactions between the cellular and humoral immune responses in Drosophila . Curr Biol 10 : 781 784.
126. Nehme NT,, Quintin J,, Cho JH,, Lee J,, Lafarge MC,, Kocks C,, Ferrandon D . 2011. Relative roles of the cellular and humoral responses in the Drosophila host defense against three Gram-positive bacterial infections. PLoS One 6 : e14743. doi:10.1371/journal.pone.0014743.
127. Basset A,, Khush RS,, Braun A,, Gardan L,, Boccard F,, Hoffmann JA,, Lemaitre B . 2000. The phytopathogenic bacteria Erwinia carotovora infects Drosophila and activates an immune response. Proc Natl Acad Sci U S A 97 : 3376 3381.
128. Shia AK,, Glittenberg M,, Thompson G,, Weber AN,, Reichhart JM,, Ligoxygakis P . 2009. Toll-dependent antimicrobial responses in Drosophila larval fat body require Spätzle secreted by haemocytes. J Cell Sci 122 : 4505 4515.
129. Foley E,, O’Farrell PH . 2003. Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in Drosophila . Genes Dev 17 : 115 125.
130. Wu SC,, Liao CW,, Pan RL,, Juang JL . 2012. Infection-induced intestinal oxidative stress triggers organ-to-organ immunological communication in Drosophila . Cell Host Microbe 11 : 410 417.
131. Glittenberg MT,, Kounatidis I,, Christensen D,, Kostov M,, Kimber S,, Roberts I,, Ligoxygakis P . 2011. Pathogen and host factors are needed to provoke a systemic host response to gastrointestinal infection of Drosophila larvae by Candida albicans . Dis Model Mech 4 : 515 525.
132. Parisi F,, Stefanatos RK,, Strathdee K,, Yu Y,, Vidal M . 2014. Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of Toll and Eiger/TNF signaling. Cell Rep 6 : 855 867.
133. Braun A,, Hoffmann JA,, Meister M . 1998. Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes. Proc Natl Acad Sci U S A 95 : 14337 14342.
134. Ruhf ML,, Braun A,, Papoulas O,, Tamkun JW,, Randsholt N,, Meister M . 2001. The domino gene of Drosophila encodes novel members of the SWI2/SNF2 family of DNA-dependent ATPases, which contribute to the silencing of homeotic genes. Development 128 : 1429 1441.
135. Gateff E . 1994. Tumor suppressor and overgrowth suppressor genes of Drosophila melanogaster: developmental aspects. Int J Dev Biol 38 : 565 590.
136. Brennan CA,, Delaney JR,, Schneider DS,, Anderson KV . 2007. Psidin is required in Drosophila blood cells for both phagocytic degradation and immune activation of the fat body. Curr Biol 17 : 67 72.
137. Irving P,, Ubeda JM,, Doucet D,, Troxler L,, Lagueux M,, Zachary D,, Hoffmann JA,, Hetru C,, Meister M . 2005. New insights into Drosophila larval haemocyte functions through genome-wide analysis. Cell Microbiol 7 : 335 350.
138. Nam HJ,, Jang IH,, Asano T,, Lee WJ . 2008. Involvement of pro-phenoloxidase 3 in lamellocyte-mediated spontaneous melanization in Drosophila . Mol Cells 26 : 606 610.
139. Waltzer L,, Ferjoux G,, Bataille L,, Haenlin M . 2003. Cooperation between the GATA and RUNX factors Serpent and Lozenge during Drosophila hematopoiesis. EMBO J 22 : 6516 6525.
140. Dudzic JP,, Kondo S,, Ueda R,, Bergman CM,, Lemaitre B . 2015. Drosophila innate immunity: regional and functional specialization of prophenoloxidases. BMC Biol 13 : 81. doi:10.1186/s12915-015-0193-6.
141. Leclerc V,, Pelte N,, El Chamy L,, Martinelli C,, Ligoxygakis P,, Hoffmann JA,, Reichhart JM . 2006. Prophenoloxidase activation is not required for survival to microbial infections in Drosophila . EMBO Rep 7 : 231 235.
142. Tang H,, Kambris Z,, Lemaitre B,, Hashimoto C . 2006. Two proteases defining a melanization cascade in the immune system of Drosophila . J Biol Chem 281 : 28097 28104.
143. Rizki TM,, Rizki RM,, Bellotti RA . 1985. Genetics of a Drosophila phenoloxidase. Mol Gen Genet 201 : 7 13.
144. Ayres JS,, Schneider DS . 2008. A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections. PLoS Biol 6 : 2764 2773.
145. Lemaitre B,, Kromer-Metzger E,, Michaut L,, Nicolas E,, Meister M,, Georgel P,, Reichhart JM,, Hoffmann JA . 1995. A recessive mutation, immune deficiency ( imd), defines two distinct control pathways in the Drosophila host defense. Proc Natl Acad Sci U S A 92 : 9465 9469.
146. Neyen C,, Binggeli O,, Roversi P,, Bertin L,, Sleiman MB,, Lemaitre B . 2015. The Black cells phenotype is caused by a point mutation in the Drosophila pro-phenoloxidase 1 gene that triggers melanization and hematopoietic defects. Dev Comp Immunol 50 : 166 174.
147. Binggeli O,, Neyen C,, Poidevin M,, Lemaitre B . 2014. Prophenoloxidase activation is required for survival to microbial infections in Drosophila . PLoS Pathog 10 : e1004067. doi:10.1371/journal.ppat.1004067.
148. Nam HJ,, Jang IH,, You H,, Lee KA,, Lee WJ . 2012. Genetic evidence of a redox-dependent systemic wound response via Hayan protease-phenoloxidase system in Drosophila . EMBO J 31 : 1253 1265.
149. Scherfer C,, Karlsson C,, Loseva O,, Bidla G,, Goto A,, Havemann J,, Dushay MS,, Theopold U . 2004. Isolation and characterization of hemolymph clotting factors in Drosophila melanogaster by a pullout method. Curr Biol 14 : 625 629.
150. 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.
151. Goto A,, Kumagai T,, Kumagai C,, Hirose J,, Narita H,, Mori H,, Kadowaki T,, Beck K,, Kitagawa Y . 2001. A Drosophila haemocyte-specific protein, hemolectin, similar to human von Willebrand factor. Biochem J 359 : 99 108.
152. Evans IR,, Wood W . 2014. Drosophila blood cell chemotaxis. Curr Opin Cell Biol 30 : 1 8.
153. Stramer B,, Wood W,, Galko MJ,, Redd MJ,, Jacinto A,, Parkhurst SM,, Martin P . 2005. Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration. J Cell Biol 168 : 567 573.
154. Wood W,, Faria C,, Jacinto A . 2006. Distinct mechanisms regulate hemocyte chemotaxis during development and wound healing in Drosophila melanogaster . J Cell Biol 173 : 405 416.
155. Moreira S,, Stramer B,, Evans I,, Wood W,, Martin P . 2010. Prioritization of competing damage and developmental signals by migrating macrophages in the Drosophila embryo. Curr Biol 20 : 464 470.
156. Razzell W,, Evans IR,, Martin P,, Wood W . 2013. Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release. Curr Biol 23 : 424 429.
157. Evans IR,, Rodrigues FS,, Armitage EL,, Wood W . 2015. Draper/CED-1 mediates an ancient damage response to control inflammatory blood cell migration in vivo. Curr Biol 25 : 1606 1612.
158. Stuart LM,, Ezekowitz RA . 2008. Phagocytosis and comparative innate immunity: learning on the fly. Nat Rev Immunol 8 : 131 141.
159. Schneider I . 1972. Cell lines derived from late embryonic stages of Drosophila melanogaster . J Embryol Exp Morphol 27 : 353 365.
160. Cherry S . 2008. Genomic RNAi screening in Drosophila S2 cells: what have we learned about host-pathogen interactions? Curr Opin Microbiol 11 : 262 270.
161. Ulvila J,, Vanha-Aho LM,, Ramet M . 2011. Drosophila phagocytosis—still many unknowns under the surface. APMIS 119 : 651 662.
162. Ramet M,, Manfruelli P,, Pearson A,, Mathey-Prevot B,, Ezekowitz RA . 2002. Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli . Nature 416 : 644 648.
163. Stuart LM,, Deng J,, Silver JM,, Takahashi K,, Tseng AA,, Hennessy EJ,, Ezekowitz RA,, Moore KJ . 2005. Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain. J Cell Biol 170 : 477 485.
164. Stuart LM,, Bell SA,, Stewart CR,, Silver JM,, Richard J,, Goss JL,, Tseng AA,, Zhang A,, El Khoury JB,, Moore KJ . 2007. CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complex. J Biol Chem 282 : 27392 27401.
165. Philips JA,, Rubin EJ,, Perrimon N . 2005. Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection. Science 309 : 1251 1253.
166. Agaisse H,, Burrack LS,, Philips JA,, Rubin EJ,, Perrimon N,, Higgins DE . 2005. Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science 309 : 1248 1251.
167. Cheng LW,, Viala JP,, Stuurman N,, Wiedemann U,, Vale RD,, Portnoy DA . 2005. Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen. Proc Natl Acad Sci U S A 102 : 13646 13651.
168. Stroschein-Stevenson SL,, Foley E,, O’Farrell PH,, Johnson AD . 2006. Identification of Drosophila gene products required for phagocytosis of Candida albicans . PLoS Biol 4 : e4. doi:10.1371/journal.pbio.0040004.
169. Pearson AM,, Baksa K,, Ramet M,, Protas M,, McKee M,, Brown D,, Ezekowitz RA . 2003. Identification of cytoskeletal regulatory proteins required for efficient phagocytosis in Drosophila . Microbes Infect 5 : 815 824.
170. Nichols Z,, Vogt RG . 2008. The SNMP/CD36 gene family in Diptera, Hymenoptera and Coleoptera: Drosophila melanogaster, D. pseudoobscura, Anopheles gambiae, Aedes aegypti, Apis mellifera, and Tribolium castaneum . Insect Biochem Mol Biol 38 : 398 415.
171. Franc NC,, Dimarcq JL,, Lagueux M,, Hoffmann J,, Ezekowitz RA . 1996. Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells. Immunity 4 : 431 443.
172. Hoebe K,, Georgel P,, Rutschmann S,, Du X,, Mudd S,, Crozat K,, Sovath S,, Shamel L,, Hartung T,, Zahringer U,, Beutler B . 2005. CD36 is a sensor of diacylglycerides. Nature 433 : 523 527.
173. Talamillo A,, Herboso L,, Pirone L,, Pérez C,, González M,, Sánchez J,, Mayor U,, Lopitz-Otsoa F,, Rodriguez MS,, Sutherland JD,, Barrio R . 2013. Scavenger receptors mediate the role of SUMO and Ftz-f1 in Drosophila steroidogenesis. PLoS Genet 9 : e1003473. doi:10.1371/journal.pgen.1003473.
174. Benton R,, Vannice KS,, Vosshall LB . 2007. An essential role for a CD36-related receptor in pheromone detection in Drosophila . Nature 450 : 289 293.
175. Abrams JM,, Lux A,, Steller H,, Krieger M . 1992. Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor-mediated endocytosis. Proc Natl Acad Sci U S A 89 : 10375 10379.
176. Ramet M,, Pearson A,, Manfruelli P,, Li X,, Koziel H,, Gobel V,, Chung E,, Krieger M,, Ezekowitz RA . 2001. Drosophila scavenger receptor CI is a pattern recognition receptor for bacteria. Immunity 15 : 1027 1038.
177. Kocks C,, Cho JH,, Nehme N,, Ulvila J,, Pearson AM,, Meister M,, Strom C,, Conto SL,, Hetru C,, Stuart LM,, Stehle T,, Hoffmann JA,, Reichhart JM,, Ferrandon D,, Rämet M,, Ezekowitz RA . 2005. Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila . Cell 123 : 335 346.
178. Kurucz E,, Márkus R,, Zsámboki J,, Folkl-Medzihradszky K,, Darula Z,, Vilmos P,, Udvardy A,, Krausz I,, Lukacsovich T,, Gateff E,, Zettervall CJ,, Hultmark D,, Andó I . 2007. Nimrod, a putative phagocytosis receptor with EGF repeats in Drosophila plasmatocytes. Curr Biol 17 : 649 654.
179. Somogyi K,, Sipos B,, Penzes Z,, Ando I . 2010. A conserved gene cluster as a putative functional unit in insect innate immunity. FEBS Lett 584 : 4375 4378.
180. Chung YS,, Kocks C . 2011. Recognition of pathogenic microbes by the Drosophila phagocytic pattern recognition receptor Eater. J Biol Chem 286 : 26524 26532.
181. Chung YS,, Kocks C . 2012. Phagocytosis of bacterial pathogens. Fly (Austin) 6 : 21 25.
182. Hashimoto Y,, Tabuchi Y,, Sakurai K,, Kutsuna M,, Kurokawa K,, Awasaki T,, Sekimizu K,, Nakanishi Y,, Shiratsuchi A . 2009. Identification of lipoteichoic acid as a ligand for Draper in the phagocytosis of Staphylococcus aureus by Drosophila hemocytes. J Immunol 183 : 7451 7460.
183. Shiratsuchi A,, Mori T,, Sakurai K,, Nagaosa K,, Sekimizu K,, Lee BL,, Nakanishi Y . 2012. Independent recognition of Staphylococcus aureus by two receptors for phagocytosis in Drosophila . J Biol Chem 287 : 21663 21672.
184. Bretscher AJ,, Honti V,, Binggeli O,, Burri O,, Poidevin M,, Kurucz E,, Zsamboki J,, Ando I,, Lemaitre B . 2015. The Nimrod transmembrane receptor Eater is required for hemocyte attachment to the sessile compartment in Drosophila melanogaster . Biol Open 4 : 355 363.
185. Gumienny TL,, Brugnera E,, Tosello-Trampont AC,, Kinchen JM,, Haney LB,, Nishiwaki K,, Walk SF,, Nemergut ME,, Macara IG,, Francis R,, Schedl T,, Qin Y,, Van Aelst L,, Hengartner MO,, Ravichandran KS . 2001. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107 : 27 41.
186. Gumienny TL,, Hengartner MO . 2001. How the worm removes corpses: the nematode C. elegans as a model system to study engulfment. Cell Death Differ 8 : 564 568.
187. Freeman MR,, Delrow J,, Kim J,, Johnson E,, Doe CQ . 2003. Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function. Neuron 38 : 567 580.
188. Awasaki T,, Tatsumi R,, Takahashi K,, Arai K,, Nakanishi Y,, Ueda R,, Ito K . 2006. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis. Neuron 50 : 855 867.
189. MacDonald JM,, Beach MG,, Porpiglia E,, Sheehan AE,, Watts RJ,, Freeman MR . 2006. The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 50 : 869 881.
190. Hoopfer ED,, McLaughlin T,, Watts RJ,, Schuldiner O,, O’Leary DD,, Luo L . 2006. Wld s protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 50 : 883 895.
191. Manaka J,, Kuraishi T,, Shiratsuchi A,, Nakai Y,, Higashida H,, Henson P,, Nakanishi Y . 2004. Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. J Biol Chem 279 : 48466 48476.
192. Kurant E,, Axelrod S,, Leaman D,, Gaul U . 2008. Six-microns-under acts upstream of Draper in the glial phagocytosis of apoptotic neurons. Cell 133 : 498 509.
193. Krivtsov AV,, Rozov FN,, Zinovyeva MV,, Hendrikx PJ,, Jiang Y,, Visser JW,, Belyavsky AV . 2007. Jedi—a novel transmembrane protein expressed in early hematopoietic cells. J Cell Biochem 101 : 767 784.
194. Hamon Y,, Trompier D,, Ma Z,, Venegas V,, Pophillat M,, Mignotte V,, Zhou Z,, Chimini G . 2006. Cooperation between engulfment receptors: the case of ABCA1 and MEGF10. PLoS One 1 : e120. doi:10.1371/journal.pone.0000120.
195. Wu HH,, Bellmunt E,, Scheib JL,, Venegas V,, Burkert C,, Reichardt LF,, Zhou Z,, Farinas I,, Carter BD . 2009. Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor. Nat Neurosci 12 : 1534 1541.
196. Scheib JL,, Sullivan CS,, Carter BD . 2012. Jedi-1 and MEGF10 signal engulfment of apoptotic neurons through the tyrosine kinase Syk. J Neurosci 32 : 13022 13031.
197. Ziegenfuss JS,, Biswas R,, Avery MA,, Hong K,, Sheehan AE,, Yeung YG,, Stanley ER,, Freeman MR . 2008. Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature 453 : 935 939.
198. Nagaosa K,, Okada R,, Nonaka S,, Takeuchi K,, Fujita Y,, Miyasaka T,, Manaka J,, Ando I,, Nakanishi Y . 2011. Integrin βν-mediated phagocytosis of apoptotic cells in Drosophila embryos. J Biol Chem 286 : 25770 25777.
199. Nonaka S,, Nagaosa K,, Mori T,, Shiratsuchi A,, Nakanishi Y . 2013. Integrin αPS3/βν-mediated phagocytosis of apoptotic cells and bacteria in Drosophila . J Biol Chem 288 : 10374 10380.
200. Lettre G,, Hengartner MO . 2006. Developmental apoptosis in C. elegans: a complex CEDnario. Nat Rev Mol Cell Biol 7 : 97 108.
201. Kinchen JM,, Ravichandran KS . 2007. Journey to the grave: signaling events regulating removal of apoptotic cells. J Cell Sci 120 : 2143 2149.
202. Hsu TY,, Wu YC . 2010. Engulfment of apoptotic cells in C. elegans is mediated by integrin α/SRC signaling. Curr Biol 20 : 477 486.
203. Gottar M,, Gobert V,, Michel T,, Belvin M,, Duyk G,, Hoffmann JA,, Ferrandon D,, Royet J . 2002. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416 : 640 644.
204. Choe KM,, Werner T,, Stöven S,, Hultmark D,, Anderson KV . 2002. Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila . Science 296 : 359 362.
205. Lagueux M,, Perrodou E,, Levashina EA,, Capovilla M,, Hoffmann JA . 2000. Constitutive expression of a complement-like protein in Toll and JAK gain-of-function mutants of Drosophila . Proc Natl Acad Sci U S A 97 : 11427 11432.
206. Bou Aoun R,, Hetru C,, Troxler L,, Doucet D,, Ferrandon D,, Matt N . 2011. Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster . J Innate Immun 3 : 52 64.
207. Levashina EA,, Moita LF,, Blandin S,, Vriend G,, Lagueux M,, Kafatos FC . 2001. Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae . Cell 104 : 709 718.
208. Blandin S,, Shiao SH,, Moita LF,, Janse CJ,, Waters AP,, Kafatos FC,, Levashina EA . 2004. Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae . Cell 116 : 661 670.
209. Watson FL,, Puttmann-Holgado R,, Thomas F,, Lamar DL,, Hughes M,, Kondo M,, Rebel VI,, Schmucker D . 2005. Extensive diversity of Ig-superfamily proteins in the immune system of insects. Science 309 : 1874 1878.
210. Schmucker D,, Clemens JC,, Shu H,, Worby CA,, Xiao J,, Muda M,, Dixon JE,, Zipursky SL . 2000. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell 101 : 671 684.
211. Wojtowicz WM,, Flanagan JJ,, Millard SS,, Zipursky SL,, Clemens JC . 2004. Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell 118 : 619 633.
212. Stuart LM,, Boulais J,, Charriere GM,, Hennessy EJ,, Brunet S,, Jutras I,, Goyette G,, Rondeau C,, Letarte S,, Huang H,, Ye P,, Morales F,, Kocks C,, Bader JS,, Desjardins M,, Ezekowitz RA . 2007. A systems biology analysis of the Drosophila phagosome. Nature 445 : 95 101.
213. Armitage SA,, Sun W,, You X,, Kurtz J,, Schmucker D,, Chen W . 2014. Quantitative profiling of Drosophila melanogaster Dscam1 isoforms reveals no changes in splicing after bacterial exposure. PLoS One 9 : e108660. doi:10.1371/journal.pone.0108660.
214. Derre I,, Pypaert M,, Dautry-Varsat A,, Agaisse H . 2007. RNAi screen in Drosophila cells reveals the involvement of the Tom complex in Chlamydia infection. PLoS Pathog 3 : 1446 1458.
215. Koo IC,, Ohol YM,, Wu P,, Morisaki JH,, Cox JS,, Brown EJ . 2008. Role for lysosomal enzyme β-hexosaminidase in the control of mycobacteria infection. Proc Natl Acad Sci U S A 105 : 710 715.
216. Ulvila J,, Vanha-aho LM,, Kleino A,, Vähä-Mäkilä M,, Vuoksio M,, Eskelinen S,, Hultmark D,, Kocks C,, Hallman M,, Parikka M,, Rämet M . 2011. Cofilin regulator 14-3-3ζ is an evolutionarily conserved protein required for phagocytosis and microbial resistance. J Leukoc Biol 89 : 649 659.
217. Korolchuk VI,, Schütz MM,, Gómez-Llorente C,, Rocha J,, Lansu NR,, Collins SM,, Wairkar YP,, Robinson IM,, O’Kane CJ . 2007. Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation. J Cell Sci 120 : 4367 4376.
218. Charrière GM,, Ip WE,, Dejardin S,, Boyer L,, Sokolovska A,, Cappillino MP,, Cherayil BJ,, Podolsky DK,, Kobayashi KS,, Silverman N,, Lacy-Hulbert A,, Stuart LM . 2010. Identification of Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated muramyl dipeptide transporters. J Biol Chem 285 : 20147 20154.