1887

Chapter 1 : Invertebrate Innate Immune Defenses

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Invertebrate Innate Immune Defenses, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816872/9781555815141_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555816872/9781555815141_Chap01-2.gif

Abstract:

All metazoans are able to mount an innate immune response. Whereas invertebrate species rely solely on this type of defense, gnathostome vertebrates have developed, in addition, a sophisticated adaptive immune system centered on lymphocytes that are absent from invertebrates. Importantly, these adaptive responses require strong stimulatory signals from cells of the innate immune system, and during infections in vertebrates, both arms of defenses cross talk in their fight against invading microorganisms. This chapter reviews the currently available data from the simplest metazoan species, the and , in an attempt to trace the origin of essential elements of the innate immune system. The host defense comprises both humoral and cellular reactions. The hallmark of the humoral response is the challenge-induced synthesis, mainly by the fat-body cells, of potent antimicrobial peptides (AMPs) and their secretion into the hemolymph (blood). The best characterized member in is eater, a type I transmembrane receptor with 32 typical EGF-like repeats in its extracellular domain. Biochemical assays have allowed the in vitro reconstruction of the proteolytic cascade activated downstream of TmGNBP3, TmPGRP-SA, and TmGNBP1. This work led to the identification of the apical protease, DmModSP, acting downstream of PRRs for the activation of the Toll pathway in . Investigations of the immune reactions of several Annelid and Mollusk species have revealed a potent cellular arm of defense, involving phagocytosis, encapsulation, and production of lytic activities often referred to as natural killer-like (NK) activities.

Citation: El Chamy L, Hetru C, Hoffmann J. 2011. Invertebrate Innate Immune Defenses, p 7-20. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch1

Key Concept Ranking

Gene Expression and Regulation
0.52463764
Small Interfering RNA
0.4778227
Complement System
0.4631164
0.52463764
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Peptidoglycans as inducers of the Toll and IMD signaling pathways. Peptidoglycan (PGN) is a glucopeptide polymer consisting of long chains of alternating N-acetylglucosamine and N-acetylmuramic acid residues connected to each other by short peptide bridges. The nature of the peptide bridge varies depending on the bacterial strains. Most gram-positive bacterial PGN carries a lysine residue at the third amino acid position in the peptide stems (Lys-type PGN), that is replaced by a diaminopimelic acid residue in most gram-negative bacteria (DAP-type PGN). In sensing of Lys-type PGN and DAP-type PGN is mediated by dedicated recognition PGRPs that activate the Toll and IMD pathways, respectively. Catalytic PGRPs have a zinc-dependant amidase activity (scissors). They reduce the immune stimulatory potency of PGN by removing the peptide bridges from the sugar backbone.

Citation: El Chamy L, Hetru C, Hoffmann J. 2011. Invertebrate Innate Immune Defenses, p 7-20. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Activation of the Toll pathway during fungal and gram-positive bacterial infections. The Toll receptor is activated by a proteolytically processed form of the cytokine-like polypeptide spaetzle (present as a dimer in the hemolymph). Microbial cell wall components (right panel) interact with circulating receptors (fungal β-glucans with GNBP3; gram-positive bacterial peptidoglycan (PGN) with a PGRP-SA/GNBP1 complex). This recognition activates, via a still unidentified mechanism, a proteolytic cascade including the zymogen modular serine protease (ModSP) and the serine protease grass, leading to the activation of the spaetzle processing enzyme (SPE), which cleaves pro-spaetzle into its active Toll-ligand form. Alternatively, microbial secreted proteases (left panel) can activate the circulating zymogen persephone, which, directly or indirectly (still unknown), activates SPE to cleave pro-spaetzle.

Citation: El Chamy L, Hetru C, Hoffmann J. 2011. Invertebrate Innate Immune Defenses, p 7-20. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Characteristic structural domains of Toll and Toll9 and of mammalian TLR2.

Citation: El Chamy L, Hetru C, Hoffmann J. 2011. Invertebrate Innate Immune Defenses, p 7-20. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

The Antiviral Response in RNA interference and inducible gene reprograming are two major arms of the antiviral defense. Viral nucleic acids are recognized by the RNase III enzyme dicer 2, which activates the small interfering RNA (siRNA) pathway leading to the degradation of viral RNA. In addition, dicer 2 can trigger the inducible expression of a variety of genes via a yet unidentified signaling pathway. Among the induced genes is that encoding the cystein-rich polypeptide, which is involved in the control of the viral load. Further, a cytokine-mediated response activated upon viral infection leads to the expression of genes via the activation of the JAK/STAT pathway in neighboring cells. The mechanism controlling this antiviral-inducible response is so far unknown.

Citation: El Chamy L, Hetru C, Hoffmann J. 2011. Invertebrate Innate Immune Defenses, p 7-20. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816872.ch01
1. Agaisse, H., and, N. Perrimon. 2004. The roles of JAK/STAT signaling in Drosophila immune responses. Immunol. Rev. 198:7282.
2. Aggarwal, K., and, N. Silverman. 2008. Positive and negative regulation of the Drosophila immune response. BMB Rep. 41:267277.
3. Aggarwal, K.,, F. Rus,, C. Vriesema-Magnuson,, D. Erturk-Hasdemir,, N. Paquette, and, N. Silverman. 2008. Rudra interrupts receptor signaling complexes to negatively regulate the IMD pathway. PLoS Pathog. 4:e1000120.
4. Antonova, Y.,, K. S. Alvarez,, Y. J. Kim,, V. Kokoza, and, A. S. Raikhel. 2009. The role of NF-kappaB factor REL2 in the Aedes aegypti immune response. Insect Biochem. Mol. Biol. 39:303314.
5. Bayne, C. J. 2009. Successful parasitism of vector snail Biomphalaria glabrata by the human blood fluke (trematode) Schistosoma mansoni: a 2009 assessment. Mol. Biochem. Parasitol. 165:818.
6. Bhoj, V. G., and, Z. J. Chen. 2009. Ubiquitylation in innate and adaptive immunity. Nature 458:430437.
7. Bian, G.,, S. W. Shin,, H. M. Cheon,, V. Kokoza, and, A. S. Raikhel. 2005. Transgenic alteration of Toll immune pathway in the female mosquito Aedes aegypti. Proc. Natl. Acad. Sci. USA 102:1356813573.
8. Blandin, S. A.,, E. Marois, and, E. A. Levashina. 2008. Antimalarial responses in Anopheles gambiae: from a complement-like protein to a complement-like pathway. Cell Host Microbe 3:364374.
9. Bosch, T. C.,, R. Augustin,, F. Anton-Erxleben,, S. Fraune,, G. Hemmrich,, H. Zill,, P. Rosenstiel,, G. Jacobs,, S. Schreiber,, M. Leippe,, M. Stanisak,, J. Grötzinger,, S. Jung,, R. Podschun,, J. Bartels,, J. Harder, and, J. M. Schröder. 2009. Uncovering the evolutionary history of innate immunity: the simple metazoan Hydra uses epithelial cells for host defence. Dev. Comp Immunol. 33:559569.
10. Buchon, N.,, M. Poidevin,, H. M. Kwon,, A. Guillou,, V. Sottas,, B. L. Lee, and, B. Lemaitre. 2009. A single modular serine protease integrates signals from pattern-recognition receptors upstream of the Drosophila Toll pathway. Proc. Natl. Acad. Sci. USA 106:1244212447.
11. Cerenius, L., and, K. Soderhall. 2004. The prophenoloxidase-activating system in invertebrates. Immunol. Rev. 198:116126.
12. Charroux, B.,, T. Rival,, K. Narbonne-Reveau, and, J. Royet. 2009. Bacterial detection by Drosophila peptidoglycan recognition proteins. Microbes Infect. 11:631636.
13. Charroux, B., and, J. Royet. 2009. Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the Drosophila immune response. Proc. Natl. Acad. Sci. USA 106:97979802.
14. Cheng-Hua, L.,, Z. Jian-Min, and, S. Lin-Sheng. 2009. A review of advances in research on marine molluscan antimicrobial peptides and their potential application in aquaculture. Molluscan Research 29:1726.
15. Christophides, G. K.,, D. Vlachou, and, F. C. Kafatos. 2004. Comparative and functional genomics of the innate immune system in the malaria vector Anopheles gambiae. Immunol. Rev. 198:127148.
16. Christophides, G. K.,, E. Zdobnov,, C. Barillas-Mury,, E. Birney,, S. Blandin,, C. Blass,, P. T. Brey,, F. H. Collins,, A. Danielli,, G. Dimopoulos,, C. Hetru,, N. T. Hoa,, J. A. Hoffmann,, S. M. Kanzok,, I. Letunic,, E. A. Levashina,, T. G. Loukeris,, G. Lycett,, S. Meister,, K. Michel,, L. F. Moita,, H. M. Müller,, M. A. Osta,, S. M. Paskewitz,, J. M. Reichhart,, A. Rzhetsky,, L. Troxler,, K. D. Vernick,, D. Vlachou,, J. Volz,, C. von Mering,, J. Xu,, L. Zheng,, P. Bork and, F. C. Kafatos. 2002. Immunity-related genes and gene families in Anopheles gambiae. Science 298:159165.
17. Davidson, C. R.,, N. M. Best,, J. W. Francis,, E. L. Cooper, and, T. C. Wood. 2008. Toll-like receptor genes (TLRs) from Capitella capitata and Helobdella robusta (Annelida). Dev. Comp. Immunol. 32:608612.
18. Defaye, A.,, I. Evans,, M. Crozatier,, W. Wood,, B. Lemaitre, and, F. Leulier. 2009. Genetic ablation of Drosophila phagocytes reveals their contribution to both development and resistance to bacterial infection. J. Innate Immun. 1:322334.
19. El Chamy, L.,, V. Leclerc,, I. Caldelari, and, J. M. Reichhart. 2008. Sensing of ‘danger signals’ and pathogen-associated molecular patterns defines binary signaling pathways ‘upstream’ of Toll. Nat. Immunol. 9:11651170.
20. Erturk-Hasdemir, D.,, M. Broemer,, F. Leulier,, W. S. Lane,, N. Paquette,, D. Hwang,, C. H. Kim,, S. Stöven,, P. Meier, and, N. Silverman. 2009. Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proc. Natl. Acad. Sci. USA 106:97799784.
21. Escoubas, J. M.,, L. Briant,, C. Montagnani,, S. Hez,, C. Devaux, and, P. Roch. 1999. Oyster IKK-like protein shares structural and functional properties with its mammalian homologues. FEBS Lett. 453:293298.
22. Evans, J. D.,, K. Aronstein,, Y. P. Chen,, C. Hetru,, J. L. Imler,, H. Jiang,, M. Kanost,, G. J. Thompson,, Z. Zou, and, D. Hultmark. 2006. Immune pathways and defence mechanisms in honey bees Apis mellifera. Insect Mol. Biol. 15:645656.
23. Fan, Z. H.,, X. M. Wang,, J. Lu,, B. Ho, and, J. L. Ding. 2008. Elucidating the function of an ancient NF-kappaB p100 homologue, CrRelish, in antibacterial defense. Infect. Immun. 76:664670.
24. Ferrandon, D.,, J. L. Imler,, C. Hetru, and, J. A. Hoffmann. 2007. The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat. Rev. Immunol. 7:862874.
25. Gauthier, M., and, B. M. Degnan. 2008. The transcription factor NF-kappaB in the demosponge Amphimedon queenslandica: insights on the evolutionary origin of the Rel homology domain. Dev. Genes Evol. 218:2332.
26. Georgel, P.,, S. Naitza,, C. Kappler,, D. Ferrandon,, D. Zachary,, C. Swimmer,, C. Kopczynski,, G. Duyk,, J. M. Reichhart, and, J. A. Hoffmann. 2001. Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis. Dev. Cell 1:503514.
27. Goodson, M. S.,, M. Kojadinovich,, J. V. Troll,, T. E. Scheetz,, T. L. Casavant,, M. B. Soares, and, M. J. McFall-Ngai. 2005. Identifying components of the NF-kappaB pathway in the beneficial Euprymna scolopes-Vibrio fischeri light organ symbiosis. Appl. Environ. Microbiol. 71:69346946.
28. Goto, A. K. Matsushita,, V. Gesellchen,, L. El Chamy,, D. Kuttenkeuler,, O. Takeuchi,, J. A. Hoffmann,, S. Akira,, M. Boutros, and, J. M. Reichhart. 2008. Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in Drosophila and mice. Nat. Immunol. 9:97104.
29. Gottar, M. V. Gobert,, A. A. Matskevich,, J. M. Reichhart,, C. Wang,, T. M. Butt,, M. Belvin,, J. A. Hoffmann, and, D. Ferrandon. 2006. Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell 127:14251437.
30. Ha, E. M. K. A. Lee,, S. H. Park,, S. H. Kim,, H. J. Nam,, H. Y. Lee,, D. Kang, and, W. J. Lee. 2009. Regulation of DUOX by the Galphaqphospholipase Cbeta-Ca2+ pathway in Drosophila gut immunity. Dev. Cell 16:386397.
31. Hemmrich, G.,, D. J. Miller, and, T. C. Bosch. 2007. The evolution of immunity: a low-life perspective. Trends Immunol. 28:449454.
32. Hoffmann, J. A. 2003. The immune response of Drosophila. Nature 426:3338.
33. Imler, J. L., and, P. Bulet. 2005. Antimicrobial peptides in Drosophila: structures, activities and gene regulation. Chem. Immunol. Allergy 86:121.
34. Inamori, K.,, S. Ariki, and, S. Kawabata. 2004. A Toll-like receptor in horseshoe crabs. Immunol. Rev. 198:106115.
35. Iwanaga,, S., and B. L. Lee. 2005. Recent advances in the innate immunity of invertebrate animals. J. Biochem. Mol. Biol. 38:128150.
36. Janeway, C. A., Jr. 1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 54 Pt 1:113.
37. Jiang, Y., and, X. Wu. 2007. Characterization of a Rel\NF-kappaB homologue in a gastropod abalone, Haliotis diversicolor supertexta. Dev. Comp. Immunol. 31:121131.
38. Kawai, T., and, S. Akira. 2009. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int. Immunol. 21:317337.
39. Kemp, C., and, J. L. Imler. 2009. Antiviral immunity in Drosophila. Curr. Opin. Immunol. 21:39.
40. Khalturin, K.,, Z. Panzer,, M. D. Cooper, and, T. C. Bosch. 2004. Recognition strategies in the innate immune system of ancestral chordates. Mol. Immunol. 41:10771087.
41. Kim, D. H., and, F. M. Ausubel. 2005. Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans. Curr. Opin. Immunol. 17:410.
42. Kimura, A.,, E. Sakaguchi, and, M. Nonaka. 2009. Multicomponent complement system of Cnidaria: C3, Bf, and MASP genes expressed in the endodermal tissues of a sea anemone, Nematostella vectensis. Immunobiology 214:165178.
43. Kleino, A.,, H. Myllymaki,, J. Kallio,, L. M. Vanhaaho,, K. Oksanen,, J. Ulvila,, D. Hultmark,, S. Valanne, and, M. Ramet. 2008. Pirk is a negative regulator of the Drosophila Imd pathway. J. Immunol. 180:54135422.
44. Kurata, S.,, S. Ariki, and, S. Kawabata. 2006. Recognition of pathogens and activation of immune responses in Drosophila and horseshoe crab innate immunity. Immunobiology 211:237249.
45. Lemaitre, B., and, J. Hoffmann. 2007. The host defense of Drosophila melanogaster. Annu. Rev. Immunol. 25:697743.
46. Leulier, F., and, B. Lemaitre. 2008. Toll-like receptors—taking an evolutionary approach. Nat. Rev. Genet. 9:165178.
47. Lhocine, N.,, P. S. Ribeiro,, N. Buchon,, A. Wepf,, R. Wilson,, T. Tenev,, B. Lemaitre,, M. Gstaiger,, P. Meier, and, F. Leulier. 2008. PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host Microbe 4:147158.
48. Maillet, F.,, V. Bischoff, C. Vignal,, J. Hoffmann, and, J. Royet. 2008. The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation. Cell Host Microbe 3:293303.
49. Meister, M. 2004. Blood cells of Drosophila: cell lineages and role in host defence. Curr. Opin. Immunol. 16:1015.
50. Meister, S.,, S. M. Kanzok,, X. L. Zheng,, C. Luna,, T. R. Li,, N. T. Hoa,, J. R. Clayton,, K. P. White,, F. C. Kafatos,, G. K. Christophides, and, L. Zheng. 2005. Immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito Anopheles gambiae. Proc. Natl. Acad. Sci. USA 102:1142011425.
51. Montagnani, C.,, C. Kappler,, J. M. Reichhart, and, J. M. Escoubas. 2004. Cg-Rel, the first Rel/NF-kappaB homolog characterized in a mollusk, the Pacific oyster Crassostrea gigas. FEBS Lett. 561:7582.
52. Pancer, Z.,, C. T. Amemiya,, G. R. Ehrhardt,, J. Ceitlin,, G. L. Gartland, and, M. D. Cooper. 2004. Somatic diversification of variable lymphocyte receptors in the Agnathan sea lamprey. Nature 430:174180.
53. Qiu, L.,, L. Song,, W. Xu,, D. Ni, and, Y. Yu. 2007. Molecular cloning and expression of a Toll receptor gene homologue from Zhikong Scallop, Chlamys farreri. Fish Shellfish Immunol. 22:451466.
54. Qiu, L.,, L. Song,, Y. Yu,, W. Xu,, D. Ni, and, Q. Zhang. 2007. Identification and characterization of a myeloid differentiation factor 88 (MyD88) cDNA from Zhikong scallop Chlamys farreri. Fish Shellfish Immunol. 23:614623.
55. Rast, J. P., and, C. Messier-Solek. 2008. Marine invertebrate genome sequences and our evolving understanding of animal immunity. Biol. Bull. 214:274283.
56. Roh, K. B.,, C. H. Kim,, H. Lee,, H. M. Kwon,, J. W. Park,, J. H. Ryu,, K. Kurokawa,, N. C. Ha,, W. J. Lee,, B. Lemaitre,, K. Soderhall, and, B. L. Lee. 2009. Proteolytic cascade for the activation of the insect toll pathway induced by the fungal cell wall component. J. Biol. Chem. 284:1947419481.
57. Royet, J.,, J. M. Reichhart, and, J. A. Hoffmann. 2005. Sensing and signaling during infection in Drosophila. Curr. Opin. Immunol. 17:1117.
58. Ryu, J. H.,, S. H. Kim,, H. Y. Lee,, J. Y. Bai,, Y. D. Nam,, J. W. Bae,, D. G. Lee,, S. C. Shin,, E. M. Ha, and, W. J. Lee. 2008. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319:777782.
59. Sackton, T. B.,, B. P. Lazzaro,, T. A. Schlenke,, J. D. Evans,, D. Hultmark, and, A. G. Clark. 2007. Dynamic evolution of the innate immune system in Drosophila. Nat. Genet. 39:14611468.
60. Salzet, M.,, A. Tasiemski, and, E. Cooper. 2006. Innate immunity in lophotrochozoans: the annelids. Curr. Pharm. Des. 12:30433050.
61. Schulenburg, H.,, C. L. Kurz, and, J. J. Ewbank. 2004. Evolution of the innate immune system: the worm perspective. Immunol. Rev. 198:3658.
62. Shin, S. W.,, V. Kokoza,, G. Bian,, H. M. Cheon,, Y. J. Kim, and, A. S. Raikhel. 2005. REL1, a homologue of Drosophila dorsal, regulates toll antifungal immune pathway in the female mosquito Aedes aegypti. J. Biol. Chem. 280:1649916507.
63. Shin, S. W.,, G. Bian, and, A. S. Raikhel. 2006. A toll receptor and a cytokine, Toll5A and Spz1C, are involved in toll antifungal immune signaling in the mosquito Aedes aegypti. J. Biol. Chem. 281:3938839395.
64. Shivers, R. P.,, M. J. Youngman, and, D. H. Kim. 2008. Transcriptional responses to pathogens in Caenorhabditis elegans. Curr. Opin. Microbiol. 11:251256.
65. Stuart, L. M., and, R. A. Ezekowitz. 2008. Phagocytosis and comparative innate immunity: learning on the fly. Nat. Rev. Immunol. 8:131141.
66. Tanaka, H.,, J. Ishibashi,, K. Fujita,, Y. Nakajima,, A. Sagisaka,, K. Tomimoto,, N. Suzuki,, M. Yoshiyama,, Y. Kaneko,, T. Iwasaki,, T. Sunagawa,, K. Yamaji,, A. Asaoka,, K. Mita, and, M. Yamakawa. 2008. A genome-wide analysis of genes and gene families involved in innate immunity of Bombyx mori. Insect Biochem. Mol. Biol. 38:10871110.
67. Tang, H.,, Z. Kambris,, B. Lemaitre, and, C. Hashimoto. 2008. A serpin that regulates immune melanization in the respiratory system of Drosophila. Dev. Cell. 15:617626.
68. Wang, X., W. N. S. Tan, B. Ho, and, J. L. Ding. 2006. Evidence for the ancient origin of the NF-kappaB/IkappaB cascade: its archaic role in pathogen infection and immunity. Proc. Natl. Acad. Sci. USA 103:42044209.
69. Wang, Y.,, T. Cheng,, S. Rayaprolu,, Z. Zou,, Q. Xia,, Z. Xiang, and, H. Jiang. 2007. Proteolytic activation of pro-spatzle is required for the induced transcription of antimicrobial peptide genes in lepidopteran insects. Dev. Comp. Immunol. 31:10021012.
70. Waterhouse R. M., E. V. Kriventseva,, S. Meister,, Z. Xi,, K. S. Alvarez,, L. C. Bartholomay,, C. Barillas-Mury,, G. Bian,, S. Blandin,, B. M. Christensen,, Y. Dong,, H. Jiang,, M. R. Kanost,, A. C. Koutsos,, E. A. Levashina,, J. Li,, P. Ligoxygakis,, R. M. Maccallum,, G. F. Mayhew,, A. Mendes,, K. Michel,, M. A. Osta,, S. Paskewitz,, S. W. Shin,, D. Vlachou,, L. Wang,, W. Wei,, L. Zheng,, Z. Zou,, D. W. Severson,, A. S. Raikhel,, F. C. Kafatos,, G. Dimopoulos,, E. M. Zdobnov, and, G. K. Christophides. 2007. Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes. Science 316:17381743.
71. Xi, Z.,, J. L. Ramirez, and, G. Dimopoulos. 2008. The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog. 4:e1000098.
72. Zhang, S. M.,, C. M. Adema,, T. B. Kepler, and, E. S. Loker. 2004. Diversification of Ig superfamily genes in an invertebrate. Science 305:251254.
73. Zhu, B.,, J. A. Pennack,, P. McQuilton,, M. G. Forero,, K. Mizuguchi,, B. Sutcliffe,, C. J. Gu,, J. C. Fenton, and, A. Hidalgo. 2008. Drosophila neurotrophins reveal a common mechanism for nervous system formation. PLoS Biol. 6:e284.
74. Zhu, Y.,, S. Thangamani,, B. Ho, and, J. L. Ding. 2005. The ancient origin of the complement system. EMBO J. 24:382394.
75. Zou, Z.,, J. D. Evans,, Z. Lu,, P. Zhao,, M. Williams,, N. Sumathipala,, C. Hetru,, D. Hultmark, and, H. Jiang. 2007. Comparative genomic analysis of the Tribolium immune system. Genome Biol. 8:R177.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error