Insects mount a robust innate immune response against a wide array of microbial pathogens. For example, the fruit fly Drosphila melanogaster uses both cellular and humoral innate immune responses to combat pathogens. The hallmark of the Drosophila humoral immune response is the rapid induction of antimicrobial peptide genes in the fat body, the homolog of the mammalian liver. Expression of these antimicrobial peptide genes is rapidly induced by two immune signaling pathways, which respond to distinct microorganisms. The Toll pathway is activated by fungal and Gram-positive bacterial infections, whereas the IMD pathway responds to Gram-negative bacteria. In this chapter, we discuss recent advances in understanding the mechanisms involved in microbial recogni-tion, signal transduction, and immune protection mediated by these pathways, highlighting similarities and differences between Drosophila immune responses and mammalian innate immunity.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
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
Akimaru H, Hou DX, Ishii S (1997) Drosophila CBP is required for dorsal-dependent twist gene expression. Nat Genet 17:211–214
Asling B, Dushay MS, Hultmark D (1995) Identification of early genes in the Drosophila immune response by PCR-based differential display: the Attacin A gene and the evolution of attacin-like proteins. Insect Biochem Mol Biol 25:511–518
Avila A, Silverman N, Diaz-Meco MT, Moscat J (2002) The Drosophila atypical protein kinase C-ref(2) p complex constitutes a conserved module for signaling in the toll pathway. Mol Cell Biol 22:8787–8795
Baeg GH, Zhou R, Perrimon N (2005) Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes Dev 19:1861–1870
Belvin MP, Jin Y, Anderson KV (1995) Cactus protein degradation mediates Drosophila dorsal-ventral signaling. Genes Dev 9:783–793
Bergmann A, Stein D, Geisler R, Hagenmaier S, Schmid B, Fernandez N, Schnell B, Nusslein-Volhard C (1996) A gradient of cytoplasmic Cactus degradation establishes the nuclear localization gradient of the dorsal morphogen in Drosophila. Mech Dev 60:109–123
Binari R, Perrimon N (1994) Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. Genes Dev 8:300–312
Bischoff V, Vignal C, Boneca IG, Michel T, Hoffmann JA, Royet J (2004) Function of the Drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat Immunol 5:1175–1180
Bischoff V, Vignal C, Duvic B, Boneca IG, Hoffmann JA, Royet J (2006) Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. PLoS Pathog 2:e14
Boman HG, Nilsson I, Rasmuson B (1972) Inducible antibacterial defence system in Drosophila. Nature 237:232–235
Boutros M, Agaisse H, Perrimon N (2002) Sequential activation of signaling pathways during innate immune responses in Drosophila. Dev Cell 3:711–722
Brennan CA, Anderson KV (2004) Drosophila: the genetics of innate immune recognition and response. Annu Rev Immunol 22:457–483
Brey PT (1998) The contributions of the Pasteur school of insect immunity in molecular mechanisms of immune responses in insects. Chapman & Hall, London
Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–851
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
Cha GH, Cho KS, Lee JH, Kim M, Kim E, Park J, Lee SB, Chung J (2003) Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c-Jun N-terminal kinase and NF-kappaB-dependent signaling pathways. Mol Cell Biol 23:7982–7991
Chang CI, Ihara K, Chelliah Y, Mengin-Lecreulx D, Wakatsuki S, Deisenhofer J (2005) Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition. Proc Natl Acad Sci USA 102:10279–10284
Chang CI, Chelliah Y, Borek D, Mengin-Lecreulx D, Deisenhofer J (2006) Structure of trachael cytotoxin in complex with a heterodimeric pattern-recognition receptor. Science 311:1761–1764
Chaves-Carballo E (2005) Carlos Finlay and yellow fever: triumph over adversity. Mil Med 170:881–885
Chen FE, Huang DB, Chen YQ, Ghosh G (1998a) Crystal structure of p50/p65 heterodimer of transcription factor NF-kappaB bound to DNA. Nature 391:410–413
Chen W, White MA, Cobb MH (2002) Stimulus-specific requirements for MAP3 kinases in activating the JNK pathway. J Biol Chem 277:49105–49110
Chen YQ, Ghosh S, Ghosh G (1998b) A novel DNA recognition mode by the NF-kappa B p65 homodimer. Nat Struct Biol 5:67–73
Cherry S, Silverman N (2006) Host–pathogen interactions in Drosophila: new tricks from an old friend. Nat Immunol 7:911–917
Cho JH, Fraser IP, Fukase K, Kusumoto S, Fujimoto Y, Stahl GL, Ezekowitz RAB (2005) Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity. Blood 106:2551–2558
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
Choe KM, Lee H, Anderson KV (2005) Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor. Proc Natl Acad Sci USA 102:1122–1126
Cookson BT, Cho HL, Herwaldt LA, Goldman WE (1989) Biological activities and chemical composition of purified tracheal cytotoxin of Bordetella pertussis. Infect Immun 57:2223–2229
De Gregorio E, Spellman PT, Rubin GM, Lemaitre B (2001) Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc Natl Acad Sci USA 98:12590–12595
De Gregorio E, Han SJ, Lee WJ, Baek MJ, Osaki T, Kawabata S, Lee BL, Iwanaga S, Lemaitre B, Brey PT (2002a) An immune-responsive Serpin regulates the melanization cascade in Drosophila. Dev Cell 3:581–592
De Gregorio E, Spellman PT, Tzou P, Rubin GM, Lemaitre B (2002b) The Toll and IMD pathways are the major regulators of the immune response in Drosophila. EMBO J 21:2568–2579
Delaney JR, Stoven S, Uvell H, Anderson KV, Engstrom Y, Mlodzik M (2006) Cooperative control of Drosophila immune responses by the JNK and NF-kappaB signaling pathways. EMBO J 25:3068–3077
Dimarcq JL, Hoffmann D, Meister M, Bulet P, Lanot R, Reichhart JM, Hoffmann JA (1994) Characterization and transcriptional profiles of a Drosophila gene encoding an insect defensin. A study in insect immunity. Eur J Biochem 221:201–209
Dong Y, Taylor HE, Dimopoulos G (2006) AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles gambiae innate immune system. PLoS Biol 4:e229
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
Drier EA, Steward R (1997) The dorsoventral signal transduction pathway and the Rel-like transcription factors in Drosophila. Semin Cancer Biol 8:83–92
Drier EA, Huang LH, Steward R (1999) Nuclear import of the Drosophila Rel protein Dorsal is regulated by phosphorylation. Genes Dev 13:556–568
Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, Yang K, Chapgier A, Eidenschenk C, Eid P, et al (2003) Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 33:388–391
Dushay MS, Åsling B, Hultmark D (1996) Origins of immunity: Relish, a compound Rel-like gene in the antibacterial defense of Drosophila. Proc Natl Acad Sci USA 93:10343–10347
Dutta J, Fan Y, Gupta N, Fan G, Gelinas C (2006) Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene 25:6800–6816
Dziarski R, Platt KA, Gelius E, Steiner H, Gupta D (2003) Defect in neutrophil killing and increased susceptibility to infection with non-pathogenic Gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)-deficient mice. Blood 102:689–697
Ekengren S, Hultmark D (1999) Drosophila cecropin as an antifungal agent. Insect Biochem Mol Biol 29:965–972
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
Engstrom Y, Kadalayil L, Sun SC, Samakovlis C, Hultmark D, Faye I (1993) kappa B-like motifs regulate the induction of immune genes in Drosophila. J Mol Biol 232:327–333
Fernandez NQ, Grosshans J, Goltz JS, Stein D (2001) Separable and redundant regulatory determinants in Cactus mediate its dorsal group dependent degradation. Development 128:2963–2974
Ferrandon D, Jung AC, Criqui M, Lemaitre B, Uttenweiler-Joseph S, Michaut L, Reichhart J, Hoffmann JA (1998) A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J 17:1217–1227
Filipe SR, Tomasz A, Ligoxygakis P (2005) Requirements of peptidoglycan structure that allow detection by the Drosophila Toll pathway. EMBO Rep 6:327–333
Fritz JH, Le Bourhis L, Sellge G, Magalhaes JG, Fsihi H, Kufer TA, Collins C, Viala J, Ferrero RL, Girardin SE, Philpott DJ (2007) Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity 26:445– 459
Geisler R, Bergmann A, Hiromi Y, Nusslein-Volhard C (1992) cactus, a gene involved in dorsoventral pattern formation of Drosophila, is related to the I kappa B gene family of vertebrates. Cell 71:613–621
Gelius E, Persson C, Karlsson J, Steiner H (2003) A mammalian peptidoglycan recognition protein with N-acetylmuramoyl-L-alanine amidase activity. Biochem Biophys Res Commun 306:988–994
Georgel P, Naitza S, Kappler C, Ferrandon D, Zachary D, Swimmer C, Kopczynski C, Duyk G, Reichhart JM, Hoffmann JA (2001) Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis. Dev Cell 1:503–514
Gesellchen V, Kuttenkeuler D, Steckel M, Pelte N, Boutros M (2005) An RNA interference screen identifies Inhibitor of Apoptosis Protein 2 as a regulator of innate immune signalling in Drosophila. EMBO Rep 6:979–984
Gillespie SK, Wasserman SA (1994) Dorsal, a Drosophila Rel-like protein, is phosphorylated upon activation of the transmembrane protein Toll. Mol Cell Biol 14:3559–3568
Gobert V, Gottar M, Matskevich AA, Rutschmann S, Royet J, Belvin M, Hoffmann JA, Ferrandon D (2003) Dual activation of the Drosophila Toll pathway by two pattern recognition receptors. Science 302:2126–2130
Goldman WE, Klapper DG, Baseman JB (1982) Detection, isolation, and analysis of a released Bordetella pertussis product toxic to cultured tracheal cells. Infect Immun 36:782–794
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
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
Gross I, Georgel P, Kappler C, Reichhart JM, Hoffmann JA (1996) Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin. Nucleic Acids Res 24:1238–1245
Guan R, Mariuzza RA (2007) Peptidoglycan recognition proteins of the innate immune system. Trends Microbiol 15:127–134
Hayden MS, West AP, Ghosh S (2006) NF-kappaB and the immune response. Oncogene 25:6758–6780
Hedengren M, Åsling B, Dushay MS, Ando I, Ekengren S, Wihlborg M, Hultmark D (1999) Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. Mol Cell 4:827–837
Heimpel AM, Harshbarger JC (1965) Symposium on microbial insecticides. V. Immunity in insects. Bacteriol Rev 29:397–405
Holland PM, Suzanne M, Campbell JS, Noselli S, Cooper JA (1997) MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous. J Biol Chem 272:24994–24998
Hombria JC, Brown S (2002) The fertile field of Drosophila Jak/STAT signalling. Curr Biol 12:R569–R575
Hou XS, Melnick MB, Perrimon N (1996) Marelle acts downstream of the Drosophila HOP/JAK kinase and encodes a protein similar to the mammalian STATs. Cell 84:411– 419
Hu X, Yagi Y, Tanji T, Zhou S, Ip YT (2004) Multimerization and interaction of Toll and Spatzle in Drosophila. Proc Natl Acad Sci USA 101:9369–9374
Huh JR, Foe I, Muro I, Chen CH, Seol JH, Yoo SJ, Guo M, Park JM, Hay BA (2007) The Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispensable for cell survival, required for the innate immune response to gram-negative bacterial infection, and can be negatively regulated by the reaper/hid/grim family of IAP-binding apoptosis inducers. J Biol Chem 282:2056–2068
Hultmark D (2003) Drosophila immunity: paths and patterns. Curr Opin Immunol 15:12–19
Hultmark D, Engstrom A, Andersson K, Steiner H, Bennich H, Boman HG (1983) Insect immunity. Attacins, a family of antibacterial proteins from Hyalophora cecropia. EMBO J 2:571–576
Ip YT, Reach M, Engstrom Y, Kadalayil L, Cai H, Gonzalez-Crespo S, Tatei K, Levine M (1993) Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell 75:753–763
Irving P, Troxler L, Heuer TS, Belvin M, Kopczynski C, Reichhart JM, Hoffmann JA, Hetru C (2001) A genome-wide analysis of immune responses in Drosophila. Proc Natl Acad Sci USA 98:15119–15124
Isoda K, Nusslein-Volhard C (1994) Disulfide cross-linking in crude embryonic lysates reveals three complexes of the Drosophila morphogen dorsal and its inhibitor cactus. Proc Natl Acad Sci USA 91:5350 –5354
Jang IH, Chosa N, Kim SH, Nam HJ, Lemaitre B, Ochiai M, Kambris Z, Brun S, Hashimoto C, Ashida M, et al (2006) A Spatzle-processing enzyme required for toll signaling activation in Drosophila innate immunity. Dev Cell 10:45–55
Kambris Z, Brun S, Jang IH, Nam HJ, Romeo Y, Takahashi K, Lee WJ, Ueda R, Lemaitre B (2006) Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine proteases required for Toll activation. Curr Biol 16:808–813
Kaneko T, Goldman WE, Mellroth P, Steiner H, Fukase K, Kusumoto S, Harley W, Fox A, Golenbock D, Silverman N (2004) Monomeric and polymeric gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway. Immunity 20:637–649
Kaneko T, Yano T, Aggarwal K, Lim JH, Ueda K, Oshima Y, Peach C, Erturk-Hasdemir D, Goldman WE, Oh BH, et al (2006) PGRP-LC and PGRP-LE have essential yet distinct functions in the Drosophila immune response to monomeric DAP-type peptidoglycan. Nat Immunol 7:715–723
Kang D, Liu G, Lundstrom A, Gelius E, Steiner H (1998) A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc Natl Acad Sci USA 95:10078–10082
Kappler C, Meister M, Lagueux M, Gateff E, Hoffmann JA, Reichhart JM (1993) Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila. EMBO J 12:1561–1568
Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436
Karst SM, Wobus CE, Lay M, Davidson J, Virgin HW (2003) STAT1-dependent innate immunity to a Norwalk-like virus. Science 299:1575–1578
Khush RS, Cornwell WD, Uram JN, Lemaitre B (2002) A ubiquitin-proteasome pathway represses the Drosophila immune deficiency signaling cascade. Curr Biol 12:1728–1737
Kim MS, Byun M, Oh BH (2003) Crystal structure of peptidoglycan recognition protein LB from Drosophila melanogaster. Nat Immunol 4:787–793
Kim T, Yoon J, Cho H, Lee WB, Kim J, Song YH, Kim SN, Yoon JH, Kim-Ha J, Kim YJ (2005) Downregulation of lipopolysaccharide response in Drosophila by negative crosstalk between the AP1 and NF-kappaB signaling modules. Nat Immunol 6:211–218
Kim Y-S, Han S-J, Ryu J-H, Choi K-H, Hong Y-S, Chung Y-H, Perrot S, Raibaud A, Brey PT, Lee WJ (2000) Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells. J Biol Chem 275:2071–2079
Kleino A, Valanne S, Ulvila J, Kallio J, Myllymaki H, Enwald H, Stoven S, Poidevin M, Ueda R, Hultmark D, et al (2005) Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway. EMBO J 24:3423–3434
Koropatnick TA, Engle JT, Apicella MA, Stabb EV, Goldman WE, McFall-Ngai MJ (2004) Microbial factor-mediated development in a host–bacterial mutualism. Science 306:1186–1188
Kylsten P, Samakovlis C, Hultmark D (1990) The cecropin locus in Drosophila; a compact gene cluster involved in the response to infection. EMBO J 9:217–224
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 USA 97:11427–11432
Lemaitre B (2004) The road to Toll. Nat Rev Immunol 4:521–527
Lemaitre B, Hoffmann J (2007) The host defense of Drosophila melanogaster. Annu Rev Immunol 25:697–743
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
Lemaitre B, Reichhart JM, Hoffmann JA (1997) Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc Natl Acad Sci USA 94:14614–14619
Leulier F, Rodriguez A, Khush RS, Abrams JM, Lemaitre B (2000) The Drosophila caspase Dredd is required to resist Gram-negative bacterial infection. EMBO Rep 1:353–358
Leulier F, Parquet C, Pili-Floury S, Ryu JH, Caroff M, Lee WJ, Mengin-Lecreulx D, Lemaitre B (2003) The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat Immunol 4:478–484
Leulier F, Lhocine N, Lemaitre B, Meier P (2006) The Drosophila inhibitor of apoptosis protein DIAP2 functions in innate immunity and is essential to resist gram-negative bacterial infection. Mol Cell Biol 26:7821–7831
Levashina EA, Ohresser S, Bulet P, Reichhart JM, Hetru C, Hoffmann JA (1995) Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties. Eur J Biochem 233:694–700
Levashina EA, Langley E, Green C, Gubb D, Ashburner M, Hoffmann JA, Reichhart JM (1999) Constitutive activation of Toll-mediated antifungal defense in serpin-deficient Drosophila. Science 285:1917–1919
Liehl P, Blight M, Vodovar N, Boccard F, Lemaitre B (2006) Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog 2:e56
Ligoxygakis P, Pelte N, Hoffmann JA, Reichhart JM (2002) Activation of Drosophila Toll during fungal infection by a blood serine protease. Science 297:114 –116
Lim JH, Kim MS, Kim HE, Yano T, Oshima Y, Aggarwal K, Goldman WE, Silverman N, Kurata S, Oh BH (2006) Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins. J Biol Chem 281:8286–8295
Liu C, Gelius E, Liu G, Steiner H, Dziarski R (2000) Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth. J Biol Chem 275:24490–24499
Liu ZP, Galindo RL, Wasserman SA (1997) A role for CKII phosphorylation of the cactus PEST domain in dorsoventral patterning of the Drosophila embryo. Genes Dev 11:3413–3422
Lo D, Tynan W, Dickerson J, Mendy J, Chang HW, Scharf M, Byrne D, Brayden D, Higgins L, Evans C, O’Mahony DJ (2003) Peptidoglycan recognition protein expression in mouse Peyer’s Patch follicle associated epithelium suggests functional specialization. Cell Immunol 224:8–16
Lu X, Wang M, Qi J, Wang H, Li X, Gupta D, Dziarski R (2006) Peptidoglycan recognition proteins are a new class of human bactericidal proteins. J Biol Chem 281:5895–5907
Lu Y, Wu LP, Anderson KV (2001) The antibacterial arm of the Drosophila innate immune response requires an IkappaB kinase. Genes Dev 15:104–110
Manfruelli P, Reichhart JM, Steward R, Hoffmann JA, Lemaitre B (1999) A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF. EMBO J 18:3380–3391
Mathur P, Murray B, Crowell T, Gardner H, Allaire N, Hsu YM, Thill G, Carulli JP (2004) Murine peptidoglycan recognition proteins PglyrpIalpha and PglyrpIbeta are encoded in the epidermal differentiation complex and are expressed in epidermal and hematopoietic tissues. Genomics 83:1151–1163
Mellroth P, Steiner H (2006) PGRP-SB1: an N-acetylmuramoyl L-alanine amidase with antibacterial activity. Biochem Biophys Res Commun 350:994–999
Mellroth P, Karlsson J, Steiner H (2003) A scavenger function for a Drosophila peptidoglycan recognition protein. J Biol Chem 278:7059–7064
Melly MA, McGee ZA, Rosenthal RS (1984) Ability of monomeric peptidoglycan fragments from Neisseria gonorrhoeae to damage human fallopian-tube mucosa. J Infect Dis 149:378–386
Meng X, Khanuja BS, Ip YT (1999) Toll receptor-mediated Drosophila immune response requires Dif, an NF-kB factor. Genes Dev 13:792–797
Mengin-Lecreulx D, Lemaitre B (2005) Structure and metabolism of peptidoglycan and molecular requirements allowing its detection by the Drosophila innate immune system. J Endotoxin Res 11:105–111
Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 5:503–507
Michaut L, Fehlbaum P, Moniatte M, Van Dorsselaer A, Reichhart JM, Bulet P (1996) Determination of the disulfide array of the first inducible antifungal peptide from insects: drosomycin from Drosophila melanogaster. FEBS Lett 395:6–10
Michel T, Reichhart JM, Hoffmann JA, Royet J (2001) Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414:756–759
Muller P, Kuttenkeuler D, Gesellchen V, Zeidler MP, Boutros M (2005) Identification of JAK/STAT signalling components by genome-wide RNA interference. Nature 436:871–875
Nicolas E, Reichhart JM, Hoffmann JA, Lemaitre B (1998) In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila. J Biol Chem 273:10463–10469
Ochiai M, Ashida M (1999) A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of the silkworm, Bombyx mori. J Biol Chem 274:11854–11858
Park JM, Kim JM, Kim LK, Kim SN, Kim-Ha J, Kim JH, Kim YJ (2003) Signal-induced transcriptional activation by Dif requires the dTRAP80 mediator module. Mol Cell Biol 23:1358–1367
Park JM, Brady H, Ruocco MG, Sun H, Williams D, Lee SJ, Kato T Jr, Richards N, Chan K, Mercurio F, et al (2004) Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila. Genes Dev 18:584–594
Park JW, Kim CH, Kim JH, Je BR, Roh KB, Kim SJ, Lee HH, Ryu JH, Lim JH, Oh BH, et al (2007) Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects. Proc Natl Acad Sci USA 104:6602–6607
Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8:49–62
Perkins ND, Felzien LK, Betts JC, Leung K, Beach DH, Nabel GJ (1997) Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator. Science 275:523–527
Pham LN, Dionne MS, Shirasu-Hiza M, Schneider DS (2007) A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathog 3:e26
Pili-Floury S, Leulier F, Takahashi K, Saigo K, Samain E, Ueda R, Lemaitre B (2004) In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J Biol Chem 279:12848–12853
Qiu P, Pan PC, Govind S (1998) A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. Development 125:1909–1920
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
Reach M, Galindo RL, Towb P, Allen JL, Karin M, Wasserman SA (1996) A gradient of cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. Dev Biol 180:353–364
Reichhart JM, Meister M, Dimarcq JL, Zachary D, Hoffmann D, Ruiz C, Richards G, Hoffmann JA (1992) Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter. EMBO J 11:1469–1477
Reichhart JM, Georgel P, Meister M, Lemaitre B, Kappler C, Hoffmann JA (1993) Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila. C R Acad Sci III 316:1218–1224
Rosenthal RS (1979) Release of soluble peptidoglycan from growing gonococci: hexaminidase and amidase activities. Infect Immun 24:869–878
Roth S, Stein D, Nusslein-Volhard C (1989) A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo. Cell 59:1189–1202
Rutschmann S, Jung AC, Zhou R, Silverman N, Hoffmann JA, Ferrandon D (2000) Role of Drosophila IKK gamma in a toll-independent antibacterial immune response. Nat Immunol 1:342–347
Samakovlis C, Kimbrell DA, Kylsten P, Engstrom A, Hultmark D (1990) The immune response in Drosophila: pattern of cecropin expression and biological activity. Embo J 9:2969–2976
Samakovlis C, Åsling B, Boman HG, Gateff E, Hultmark D (1992) In vitro induction of cecropin genes–an immune response in a Drosophila blood cell line. Biochem Biophys Res Commun 188:1169–1175
Santamaria P, Nusslein-Volhard C (1983) Partial rescue of dorsal, a maternal effect mutation affecting the dorso-ventral pattern of the Drosophila embryo, by the injection of wild-type cytoplasm. EMBO J 2:1695–1699
Schleifer KH, Kandler O (1972) Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol Rev 36:407–477
Schmitz ML, Santos Silva MA dos, Baeuerle PA (1995) Transactivation domain 2 (TA2) of p65 NF-kappa B. Similarity to TA1 and phorbol ester-stimulated activity and phosphorylation in intact cells. J Biol Chem 270:15576–15584
Senger K, Armstrong GW, Rowell WJ, Kwan JM, Markstein M, Levine M (2004) Immunity regulatory DNAs share common organizational features in Drosophila. Mol Cell 13:19–32
Shen B, Liu H, Skolnik EY, Manley JL (2001) Physical and functional interactions between Drosophila TRAF2 and Pelle kinase contribute to Dorsal activation. Proc Natl Acad Sci USA 98:8596–8601
Silverman N, Zhou R, Stöven S, Pandey N, Hultmark D, Maniatis T (2000) A Drosophila IkappaB kinase complex required for Relish cleavage and antibacterial immunity. Genes Dev 14:2461–2471
Silverman N, Maniatis T (2001) NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev 15:2321–2342
Silverman N, Zhou R, Erlich RL, Hunter M, Bernstein E, Schneider D, Maniatis T (2003) Immune activation of NF-kappaB and JNK requires Drosophila TAK1. J Biol Chem 278:48928–48934
Sluss HK, Han Z, Barrett T, Davis RJ, Ip YT (1996) A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. Genes Dev 10:2745–2758
Spencer E, Jiang J, Chen ZJ (1999) Signal-induced ubiquitination of IkBa by the F-box protein Slimb/bTrCP. Genes Dev 13:284–294
Steiner H, Hultmark D, Engstrom A, Bennich H, Boman HG (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292:246–248
Steinhaus EA (1940) The microbiology of insects: with special reference to the biologic relationships between bacteria and insects. Bacteriol Rev 4:17–57
Stenbak CR, Ryu JH, Leulier F, Pili-Floury S, Parquet C, Herve M, Chaput C, Boneca IG, Lee WJ, Lemaitre B, Mengin-Lecreulx D (2004) Peptidoglycan molecular requirements allowing detection by the Drosophila immune deficiency pathway. J Immunol 173:7339–7348
Steward R (1987) Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science 238:692–694
Steward R, McNally FJ, Schedl P (1984) Isolation of the dorsal locus of Drosophila. Nature 311:262–265
Stöven S, Ando I, Kadalayil L, Engström Y, Hultmark D (2000) Activation of the Drosophila NF-kB factor Relish by rapid endoproteolytic cleavage. EMBO Rep 1:347–352
Stöven S, Silverman N, Junell A, Hedengren-Olcott M, Erturk D, Engstrom Y, Maniatis T, Hultmark D (2003) Caspase-mediated processing of the Drosophila NF-kappaB factor Relish. Proc Natl Acad Sci USA 100:5991–5996
Sun H, Bristow BN, Qu G, Wasserman SA (2002a) A heterotrimeric death domain complex in Toll signaling. Proc Natl Acad Sci USA 99:12871–12876
Sun H, Towb P, Chiem DN, Foster BA, Wasserman SA (2004) Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral patterning. EMBO J 23:100–110
Sun SC, Asling B, Faye I (1991) Organization and expression of the immunoresponsive lysozyme gene in the giant silk moth, Hyalophora cecropia. J Biol Chem 266:6644–6649
Sun X, Yin J, Starovasnik MA, Fairbrother WJ, Dixit VM (2002b) Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J Biol Chem 277:9505–9511
Swaminathan CP, Brown PH, Roychowdhury A, Wang Q, Guan R, Silverman N, Goldman WE, Boons GJ, Mariuzza RA (2006) Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs). Proc Natl Acad Sci USA 103:684–689
Takehana A, Katsuyama T, Yano T, Oshima Y, Takada H, Aigaki T, Kurata S (2002) Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae. Proc Natl Acad Sci USA 99:13705–13710
Takehana A, Yano T, Mita S, Kotani A, Oshima Y, Kurata S (2004) Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity. EMBO J 23:4690–4700
Tanji T, Hu X, Weber AN, Ip YT (2007) Toll and IMD pathways synergistically activate innate immune response in Drosophila. Mol Cell Biol 27:4578–4588
Tauszig-Delamasure S, Bilak H, Capovilla M, Hoffmann JA, Imler JL (2002) Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat Immunol 3:91–97
Towb P, Galindo RL, Wasserman SA (1998) Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila embryo. Development 125:2443–2450
Tydell CC, Yount N, Tran D, Yuan J, Selsted ME (2002) Isolation, characterization, and antimicrobial properties of bovine oligosaccharide-binding protein. A microbicidal granule protein of eosinophils and neutrophils. J Biol Chem 277:19658–19664
Tzou P, Ohresser S, Ferrandon D, Capovilla M, Reichhart JM, Lemaitre B, Hoffmann JA, Imler JL (2000) Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 13:737–748
Tzou P, Reichhart JM, Lemaitre B (2002) Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants. Proc Natl Acad Sci USA 99:2152–2157
Uehara A, Fujimoto Y, Kawasaki A, Kusumoto S, Fukase K, Takada H (2006) Meso-diaminopimelic acid and meso-lanthionine, amino acids specific to bacterial peptidoglycans, activate human epithelial cells through NOD1. J Immunol 177:1796–1804
Valanne S, Kleino A, Myllymaki H, Vuoristo J, Ramet M (2007) Iap2 is required for a sustained response in the Drosophila Imd pathway. Dev Comp Immunol (in press)
Vidal S, Khush RS, Leulier F, Tzou P, Nakamura M, Lemaitre B (2001) Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses. Genes Dev 15:1900–1912
Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351
Wang L, Weber AN, Atilano ML, Filipe SR, Gay NJ, Ligoxygakis P (2006) Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA. EMBO J 25:5005–5014
Wang ZM, Li X, Cocklin RR, Wang M, Fukase K, Inamura S, Kusumoto S, Gupta D, Dziarski R (2003) Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase. J Biol Chem 278:49044–49052
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
Weber AN, Tauszig-Delamasure S, Hoffmann JA, Lelievre E, Gascan H, Ray KP, Morse MA, Imler JL, Gay NJ (2003) Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat Immunol 4:794–800
Werner T, Liu G, Kang D, Ekengren S, Steiner H, Hultmark D (2000) A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc Natl Acad Sci USA 97:13772–13777
Werner T, Borge-Renberg K, Mellroth P, Steiner H, Hultmark D (2003) Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan. J Biol Chem 278:26319–26322
Wicker C, Reichhart JM, Hoffmann D, Hultmark D, Samakovlis C, Hoffmann JA (1990) Insect immunity. Characterization of a Drosophila cDNA encoding a novel member of the diptericin family of immune peptides. J Biol Chem 265:22493–22498
Wirth T, Baltimore D (1988) Nuclear factor NF-kappa B can interact functionally with its cognate binding site to provide lymphoid-specific promoter function. EMBO J 7:3109–3113
Wu LP, Anderson KV (1998) Regulated nuclear import of Rel proteins in the Drosophila immune response. Nature 392:93–97
Yagi Y, Ip YT (2005) Helicase89B is a Mot1p/BTAF1 homologue that mediates an antimicrobial response in Drosophila. EMBO Rep 6:1088–1094
Yan R, Small S, Desplan C, Dearolf CR, Darnell JE Jr (1996) Identification of a Stat gene that functions in Drosophila development. Cell 84:421–430
Yoshida H, Kinoshita K, Ashida M (1996) Purification of a peptidoglycan recognition protein from hemolymph of the silkworm, Bombyx mori. J Biol Chem 271:13854–13860
Zaidman-Remy A, Herve M, Poidevin M, Pili-Floury S, Kim MS, Blanot D, Oh BH, Ueda R, Mengin-Lecreulx D, Lemaitre B (2006) The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity 24:463–473
Zeidler MP, Bach EA, Perrimon N (2000) The roles of the Drosophila JAK/STAT pathway. Oncogene 19:2598–2606
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 USA 101:14192–14197
Zhang Y, Fits L van der, Voerman JS, Melief MJ, Laman JD, Wang M, Wang H, Wang M, Li X, Walls CD, et al (2005) Identification of serum N-acetylmuramoyl-l-alanine amidase as liver peptidoglycan recognition protein 2. Biochim Biophys Acta 1752:34–46
Zhou R, Silverman N, Hong M, Liao DS, Chung Y, Chen ZJ, Maniatis T (2005) The role of ubiquitnation in Drosophila innate immunity. J Biol Chem 280:34048–34055
Zhuang ZH, Sun L, Kong L, Hu JH, Yu MC, Reinach P, Zang JW, Ge BX (2006) Drosophila TAB2 is required for the immune activation of JNK and NF-kappaB. Cell Signal 18:964–970
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Ertürk-Hasdemir, D., Paquette, N., Aggarwal, K., Silverman, N. (2008). Bug Versus Bug: Humoral Immune Responses in Drosophila melanogaster . In: Heine, H. (eds) Innate Immunity of Plants, Animals, and Humans. Nucleic Acids and Molecular Biology, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73930-2_3
Download citation
DOI: https://doi.org/10.1007/978-3-540-73930-2_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-73929-6
Online ISBN: 978-3-540-73930-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)