DOI QR코드

DOI QR Code

Positive and negative regulation of the Drosophila immune response

  • Aggarwal, Kamna (Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School) ;
  • Silverman, Neal (Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School)
  • Accepted : 2008.02.25
  • Published : 2008.04.30

Abstract

Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of anti-microbial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.

Keywords

References

  1. Brennan, C. A. and Anderson, K. V. (2004) Drosophila: the genetics of innate immune recognition and response. Annu. Rev. Immunol. 22, 457-483 https://doi.org/10.1146/annurev.immunol.22.012703.104626
  2. Cherry, S. and Silverman, N. (2006) Host-pathogen interactions in drosophila: new tricks from an old friend. Nat. Immunol. 7, 911-917 https://doi.org/10.1038/ni1388
  3. Hultmark, D. (2003) Drosophila immunity: paths and patterns. Curr. Opin. Immunol. 15, 12-19 https://doi.org/10.1016/S0952-7915(02)00005-5
  4. Lemaitre, B. and Hoffmann, J. (2007) The host defense of Drosophila melanogaster. Annu. Rev. Immunol. 25, 697-743 https://doi.org/10.1146/annurev.immunol.25.022106.141615
  5. Werner, T., Liu, G., Kang, D., Ekengren, S., Steiner, H. and Hultmark, D. (2000) A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 97, 13772-13777 https://doi.org/10.1073/pnas.97.25.13772
  6. Takehana, A., Katsuyama, T., Yano, T., Oshima, Y., Takada, H., Aigaki, T. and 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. U.S.A. 99, 13705-13710. https://doi.org/10.1073/pnas.212301199
  7. Gottar, M., Gobert, V., Matskevich, A. A., Reichhart, J. M., Wang, C., Butt, T. M., Belvin, M., Hoffmann, J. A. and Ferrandon, D. (2006) Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors. Cell 127, 1425-1437 https://doi.org/10.1016/j.cell.2006.10.046
  8. Gobert, V., Gottar, M., Matskevich, A. A., Rutschmann, S., Royet, J., Belvin, M., Hoffmann, J. A. and Ferrandon, D. (2003) Dual activation of the Drosophila Toll pathway by two pattern recognition receptors. Science 302, 2126-2130 https://doi.org/10.1126/science.1085432
  9. Pili-Floury, S., Leulier, F., Takahashi, K., Saigo, K., Samain, E., Ueda, R. and 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 https://doi.org/10.1074/jbc.M313324200
  10. Bischoff, V., Vignal, C., Duvic, B., Boneca, I. G., Hoffmann, J. A. and Royet, J. (2006) Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. PLoS Pathog. 2, e14 https://doi.org/10.1371/journal.ppat.0020014
  11. Zaidman-Remy, A., Herve, M., Poidevin, M., Pili-Floury, S., Kim, M. S., Blanot, D., Oh, B. H., Ueda, R., Mengin-Lecreulx, D. and Lemaitre, B. (2006) The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity 24, 463-473 https://doi.org/10.1016/j.immuni.2006.02.012
  12. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M. and Hoffmann, J. A. (1996) The dorsoventral regulatory gene cassette Spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973-983 https://doi.org/10.1016/S0092-8674(00)80172-5
  13. Hu, X., Yagi, Y., Tanji, T., Zhou, S. and Ip, Y. T. (2004) Multimerization and interaction of Toll and Spätzle in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 101, 9369-9374. https://doi.org/10.1073/pnas.0307062101
  14. Weber, A. N., Tauszig-Delamasure, S., Hoffmann, J. A., Lelievre, E., Gascan, H., Ray, K. P., Morse, M. A., Imler, J. L. and Gay, N. J. (2003) Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat. Immunol. 4, 794-800 https://doi.org/10.1038/ni955
  15. Kambris, Z., Brun, S., Jang, I. H., Nam, H. J., Romeo, Y., Takahashi, K., Lee, W. J., Ueda, R. and 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 https://doi.org/10.1016/j.cub.2006.03.020
  16. Bischoff, V., Vignal, C., Boneca, I. G., Michel, T., Hoffmann, J. A. and Royet, J. (2004) Function of the Drosophila pattern- recognition receptor PGRP-SD in the detection of Gram-positive bacteria. Nat. Immunol. 5, 1175-1180 https://doi.org/10.1038/ni1123
  17. Michel, T., Reichhart, J. M., Hoffmann, J. A. and Royet, J. (2001) Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414, 756-759 https://doi.org/10.1038/414756a
  18. Wang, L., Weber, A. N., Atilano, M. L., Filipe, S. R., Gay, N. J. and 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 https://doi.org/10.1038/sj.emboj.7601363
  19. Levashina, E. A., Langley, E., Green, C., Gubb, D., Ashburner, M., Hoffmann, J. A. and Reichhart, J. M. (1999) Constitutive activation of Toll-mediated antifungal defense in serpin-deficient Drosophila. Science 285, 1917-1919 https://doi.org/10.1126/science.285.5435.1917
  20. Ligoxygakis, P., Pelte, N., Hoffmann, J. A. and Reichhart, J. M. (2002) Activation of Drosophila Toll during fungal infection by a blood serine protease. Science 297, 114-116 https://doi.org/10.1126/science.1072391
  21. Jang, I. H., Chosa, N., Kim, S. H., Nam, H. J., Lemaitre, B., Ochiai, M., Kambris, Z., Brun, S., Hashimoto, C., Ashida, M., Brey, P. T. and Lee, W. J. (2006) A Spatzle-processing enzyme required for toll signaling activation in Drosophila innate immunity. Dev. Cell. 10, 45-55 https://doi.org/10.1016/j.devcel.2005.11.013
  22. Sun, H., Bristow, B. N., Qu, G. and Wasserman, S. A. (2002) A heterotrimeric death domain complex in Toll signaling. Proc. Natl. Acad. Sci. U.S.A. 99, 12871-12876. https://doi.org/10.1073/pnas.202396399
  23. Tauszig-Delamasure, S., Bilak, H., Capovilla, M., Hoffmann, J. A. and Imler, J. L. (2002) Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat. Immunol. 3, 91-97 https://doi.org/10.1038/ni747
  24. Towb, P., Galindo, R. L. and Wasserman, S. A. (1998) Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila embryo. Development 125, 2443-2450
  25. Fernandez, N. Q., Grosshans, J., Goltz, J. S. and Stein, D. (2001) Separable and redundant regulatory determinants in Cactus mediate its dorsal group dependent degradation. Development 128, 2963-2974
  26. Belvin, M. P., Jin, Y. and Anderson, K. V. (1995) Cactus protein degradation mediates Drosophila dorsal-ventral signaling. Genes Dev. 9, 783-793 https://doi.org/10.1101/gad.9.7.783
  27. Bergmann, A., Stein, D., Geisler, R., Hagenmaier, S., Schmid, B., Fernandez, N., Schnell, B. and 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 https://doi.org/10.1016/S0925-4773(96)00607-7
  28. Gillespie, S. K. and Wasserman, S. A. (1994) Dorsal, a Drosophila Rel-like protein, is phosphorylated upon activation of the transmembrane protein Toll. Mol. Cell. Biol. 14, 3559-3568 https://doi.org/10.1128/MCB.14.6.3559
  29. Reach, M., Galindo, R. L., Towb, P., Allen, J. L., Karin, M. and Wasserman, S. A. (1996) A gradient of cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. Dev. Biol. 180, 353-364 https://doi.org/10.1006/dbio.1996.0308
  30. Wu, L. P. and Anderson, K. V. (1998) Regulated nuclear import of Rel proteins in the Drosophila immune response. Nature 392, 93-97 https://doi.org/10.1038/32195
  31. De Gregorio, E., Han, S. J., Lee, W. J., Baek, M. J., Osaki, T., Kawabata, S., Lee, B. L., Iwanaga, S., Lemaitre, B. and Brey, P. T. (2002) An immune-responsive Serpin regulates the melanization cascade in Drosophila. Dev. Cell. 3, 581-592 https://doi.org/10.1016/S1534-5807(02)00267-8
  32. De Gregorio, E., Spellman, P. T., Rubin, G. M. and Lemaitre, B. (2001) Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc. Natl. Acad. Sci. U.S.A. 98, 12590-12595. https://doi.org/10.1073/pnas.221458698
  33. Irving, P., Troxler, L., Heuer, T. S., Belvin, M., Kopczynski, C., Reichhart, J. M., Hoffmann, J. A. and Hetru, C. (2001) A genome-wide analysis of immune responses in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 98, 15119-15124 https://doi.org/10.1073/pnas.261573998
  34. Kaneko, T., Yano, T., Aggarwal, K., Lim, J. H., Ueda, K., Oshima, Y., Peach, C., Erturk-Hasdemir, D., Goldman, W. E., Oh, B. H., Kurata, S. and Silverman, N. (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 https://doi.org/10.1038/ni1356
  35. Choe, K. M., Werner, T., Stöven, S., Hultmark, D. and Anderson, K. V. (2002) Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science 296, 359-362 https://doi.org/10.1126/science.1070216
  36. Ramet, M., Manfruelli, P., Pearson, A., Mathey-Prevot, B. and Ezekowitz, R. A. (2002) Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature 416, 644-648 https://doi.org/10.1038/nature735
  37. Gottar, M., Gobert, V., Michel, T., Belvin, M., Duyk, G., Hoffmann, J. A., Ferrandon, D. and Royet, J. (2002) The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416, 640-644 https://doi.org/10.1038/nature734
  38. Leulier, F., Parquet, C., Pili-Floury, S., Ryu, J. H., Caroff, M., Lee, W. J., Mengin-Lecreulx, D. and Lemaitre, B. (2003) The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nat. Immunol. 4, 478-484 https://doi.org/10.1038/ni922
  39. Kaneko, T., Goldman, W. E., Mellroth, P., Steiner, H., Fukase, K., Kusumoto, S., Harley, W., Fox, A., Golenbock, D. and Silverman, N. (2004) Monomeric and polymeric Gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway. Immunity 20, 637-649 https://doi.org/10.1016/S1074-7613(04)00104-9
  40. Stenbak, C. R., Ryu, J. H., Leulier, F., Pili-Floury, S., Parquet, C., Herve, M., Chaput, C., Boneca, I. G., Lee, W. J., Lemaitre, B. and Mengin-Lecreulx, D. (2004) Peptidoglycan molecular requirements allowing detection by the Drosophila immune deficiency pathway. J. Immunol. 173, 7339-7348 https://doi.org/10.4049/jimmunol.173.12.7339
  41. Takehana, A., Yano, T., Mita, S., Kotani, A., Oshima, Y. and Kurata, S. (2004) Peptidoglycan Recognition Protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity. EMBO. J. 23, 4690-4700 https://doi.org/10.1038/sj.emboj.7600466
  42. Mellroth, P., Karlsson, J., Hakansson, J., Schultz, N., Goldman, W. E. and Steiner, H. (2005) Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in vitro. Proc. Natl. Acad. Sci. U.S.A. 102, 6455-6460. https://doi.org/10.1073/pnas.0407559102
  43. Chang, C. I., Chelliah, Y., Borek, D., Mengin-Lecreulx, D. and Deisenhofer, J. (2006) Structure of trachael cytotoxin in complex with a heterodimeric pattern-recognition receptor. Science 311, 1761-1764 https://doi.org/10.1126/science.1123056
  44. Chang, C. I., Ihara, K., Chelliah, Y., Mengin-Lecreulx, D., Wakatsuki, S. and Deisenhofer, J. (2005) Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition. Proc. Natl. Acad. Sci. U.S.A. 102, 10279-10284 https://doi.org/10.1073/pnas.0504547102
  45. Lim, J. H., Kim, M. S., Kim, H. E., Yano, T., Oshima, Y., Aggarwal, K., Goldman, W. E., Silverman, N., Kurata, S. and Oh, B. H. (2006) Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins. J. Biol. Chem. 281, 8286-8295 https://doi.org/10.1074/jbc.M513030200
  46. Choe, K. M., Lee, H. and Anderson, K. V. (2005) Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor. Proc. Natl. Acad. Sci. U.S.A. 102, 1122-1126 https://doi.org/10.1073/pnas.0404952102
  47. Meylan, E., Burns, K., Hofmann, K., Blancheteau, V., Martinon, F., Kelliher, M. and Tschopp, J. (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-${\kappa}$B activation. Nat. Immunol. 5, 503-507 https://doi.org/10.1038/ni1061
  48. Sun, X., Yin, J., Starovasnik, M. A., Fairbrother, W. J. and Dixit, V. M. (2002) Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J. Biol. Chem. 277, 9505-9511 https://doi.org/10.1074/jbc.M109488200
  49. Georgel, P., Naitza, S., Kappler, C., Ferrandon, D., Zachary, D., Swimmer, C., Kopczynski, C., Duyk, G., Reichhart, J. M. and Hoffmann, J. A. (2001) Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis. Dev. Cell. 1, 503-514 https://doi.org/10.1016/S1534-5807(01)00059-4
  50. Lu, Y., Wu, L. P. and Anderson, K. V. (2001) The antibacterial arm of the drosophila innate immune response requires an I${\kappa}$B kinase. Genes Dev. 15, 104-110 https://doi.org/10.1101/gad.856901
  51. Rutschmann, S., Jung, A. C., Zhou, R., Silverman, N., Hoffmann, J. A. and Ferrandon, D. (2000) Role of Drosophila IKK gamma in a toll-independent antibacterial immune response. Nat. Immunol. 1, 342-347 https://doi.org/10.1038/79801
  52. Silverman, N., Zhou, R., Erlich, R. L., Hunter, M., Bernstein, E., Schneider, D. and Maniatis, T. (2003) Immune activation of NF-${\kappa}$B and JNK requires Drosophila TAK1. J. Biol. Chem. 278, 48928-48934 https://doi.org/10.1074/jbc.M304802200
  53. Silverman, N., Zhou, R., Stöven, S., Pandey, N., Hultmark, D. and Maniatis, T. (2000) A Drosophila I${\kappa}B$ kinase complex required for Relish cleavage and antibacterial immunity. Genes Dev. 14, 2461-2471 https://doi.org/10.1101/gad.817800
  54. Vidal, S., Khush, R. S., Leulier, F., Tzou, P., Nakamura, M. and Lemaitre, B. (2001) Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-${\kappa}$B-dependent innate immune responses. Genes Dev. 15, 1900-1912 https://doi.org/10.1101/gad.203301
  55. Zhou, R., Silverman, N., Hong, M., Liao, D. S., Chung, Y., Chen, Z. J. and Maniatis, T. (2005) The role of ubiquitnation in Drosophila innate immunity. J. Biol. Chem. 280, 34048-34055 https://doi.org/10.1074/jbc.M506655200
  56. Pineda, G., Ea, C. K. and Chen, Z. J. (2007) Ubiquitination and TRAF signaling. Adv. Exp. Med. Biol. 597, 80-92 https://doi.org/10.1007/978-0-387-70630-6_7
  57. Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J. and Chen, Z. J. (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351 https://doi.org/10.1038/35085597
  58. Huh, J. R., Foe, I., Muro, I., Chen, C. H., Seol, J. H., Yoo, S. J., Guo, M., Park, J. M. and Hay, B. A. (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 https://doi.org/10.1074/jbc.M608051200
  59. Gesellchen, V., Kuttenkeuler, D., Steckel, M., Pelte, N. and 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 https://doi.org/10.1038/sj.embor.7400530
  60. Kleino, A., Valanne, S., Ulvila, J., Kallio, J., Myllymaki, H., Enwald, H., Stoven, S., Poidevin, M., Ueda, R., Hultmark, D., Lemaitre, B. and Ramet, M. (2005) Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway. EMBO. J. 24, 3423-3434 https://doi.org/10.1038/sj.emboj.7600807
  61. Leulier, F., Lhocine, N., Lemaitre, B. and 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 https://doi.org/10.1128/MCB.00548-06
  62. Valanne, S., Kleino, A., Myllymaki, H., Vuoristo, J. and Ramet, M. (2007) Iap2 is required for a sustained response in the Drosophila Imd pathway. Dev. Comp. Immunol. 31, 991-1001 https://doi.org/10.1016/j.dci.2007.01.004
  63. Geuking, P., Narasimamurthy, R. and Basler, K. (2005) A genetic screen targeting the tumor necrosis factor/Eiger signaling pathway: identification of Drosophila TAB2 as a functionally conserved component. Genetics 171, 1683-1694 https://doi.org/10.1534/genetics.105.045534
  64. Zhuang, Z. H., Sun, L., Kong, L., Hu, J. H., Yu, M. C., Reinach, P., Zang, J. W. and Ge, B. X. (2006) Drosophila TAB2 is required for the immune activation of JNK and NF-${\kappa}$B. Cell. Signal. 18, 964-970 https://doi.org/10.1016/j.cellsig.2005.08.020
  65. Kanayama, A., Seth, R. B., Sun, L., Ea, C. K., Hong, M., Shaito, A., Chiu, Y. H., Deng, L. and Chen, Z. J. (2004) TAB2 and TAB3 activate the NF-${\kappa}$B pathway through binding to polyubiquitin chains. Mol. Cell. 15, 535-548 https://doi.org/10.1016/j.molcel.2004.08.008
  66. Sun, L., Deng, L., Ea, C. K., Xia, Z. P. and Chen, Z. J. (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol. Cell. 14, 289-301 https://doi.org/10.1016/S1097-2765(04)00236-9
  67. Chen, W., White, M. A. and Cobb, M. H. (2002) Stimulusspecific requirements for MAP3 kinases in activating the JNK pathway. J. Biol. Chem. 277, 49105-49110 https://doi.org/10.1074/jbc.M204934200
  68. Holland, P. M., Suzanne, M., Campbell, J. S., Noselli, S. and Cooper, J. A. (1997) MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous. J. Biol. Chem. 272, 24994-24998 https://doi.org/10.1074/jbc.272.40.24994
  69. Sluss, H. K., Han, Z., Barrett, T., Davis, R. J. and Ip, Y. T. (1996) A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. Genes Dev. 10, 2745-2758 https://doi.org/10.1101/gad.10.21.2745
  70. Boutros, M., Agaisse, H. and Perrimon, N. (2002) Sequential activation of signaling pathways during innate immune responses in Drosophila. Dev. Cell. 3, 711-722 https://doi.org/10.1016/S1534-5807(02)00325-8
  71. Kim, L. K., Choi, U. Y., Cho, H. S., Lee, J. S., Lee, W. B., Kim, J., Jeong, K., Shim, J., Kim-Ha, J. and Kim, Y. J. (2007) Down-regulation of NF-${\kappa}$B target genes by the AP-1 and STAT complex during the innate immune response in Drosophila. PLoS Biology 5, e238 https://doi.org/10.1371/journal.pbio.0050238
  72. Kim, T., Yoon, J., Cho, H., Lee, W. B., Kim, J., Song, Y. H., Kim, S. N., Yoon, J. H., Kim-Ha, J. and Kim, Y. J. (2005) Downregulation of lipopolysaccharide response in Drosophila by negative crosstalk between the AP1 and NF-${\kappa}$B signaling modules. Nat. Immunol. 6, 211-218 https://doi.org/10.1038/ni1159
  73. Kallio, J., Leinonen, A., Ulvila, J., Valanne, S., Ezekowitz, R. A. and Ramet, M. (2005) Functional analysis of immune response genes in Drosophila identifies JNK pathway as a regulator of antimicrobial peptide gene expression in S2 cells. Microbes. Infect. 7, 811-819 https://doi.org/10.1016/j.micinf.2005.03.014
  74. Delaney, J. R. and Mlodzik, M. (2006) TGF-beta activated kinase-1: new insights into the diverse roles of TAK1 in development and immunity. Cell Cycle (Georgetown, Tex) 5, 2852-2855 https://doi.org/10.4161/cc.5.24.3558
  75. Stooven, S., Silverman, N., Junell, A., Hedengren-Olcott, M., Erturk, D., Engstrom, Y., Maniatis, T. and Hultmark, D. (2003) Caspase-mediated processing of the Drosophila NF-${\kappa}$B factor Relish. Proc. Natl. Acad. Sci. U.S.A. 100, 5991-5996. https://doi.org/10.1073/pnas.1035902100
  76. Stoven, S. ando, I., Kadalayil, L., Engstrom, Y. and Hultmark, D. (2000) Activation of the Drosophila NF-${\kappa}$B factor Relish by rapid endoproteolytic cleavage. EMBO. Rep. 1, 347-352 https://doi.org/10.1093/embo-reports/kvd072
  77. Leulier, F., Rodriguez, A., Khush, R. S., Abrams, J. M. and Lemaitre, B. (2000) The Drosophila caspase Dredd is required to resist Gram-negative bacterial infection. EMBO. Rep. 1, 353-358 https://doi.org/10.1093/embo-reports/kvd073
  78. Mellroth, P., Karlsson, J. and Steiner, H. (2003) A scavenger function for a Drosophila peptidoglycan recognition protein. J. Biol. Chem. 278, 7059-7064 https://doi.org/10.1074/jbc.M208900200
  79. Royet, J. and Dziarski, R. (2007) Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences. Nature Reviews 5, 264-277 https://doi.org/10.1038/nrmicro1620
  80. Werner, T., Borge-Renberg, K., Mellroth, P., Steiner, H. and 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 https://doi.org/10.1074/jbc.C300184200
  81. Garver, L. S., Wu, J. and Wu, L. P. (2006) The peptidoglycan recognition protein PGRP-SC1a is essential for Toll signaling and phagocytosis of Staphylococcus aureus in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 103, 660-665. https://doi.org/10.1073/pnas.0506182103
  82. Persson, C., Oldenvi, S. and Steiner, H. (2007) Peptidoglycan recognition protein LF: a negative regulator of Drosophila immunity. Insect. Biochem. Mol. Biol. 37, 1309-1316 https://doi.org/10.1016/j.ibmb.2007.08.003
  83. Ganguly, A., Jiang, J. and Ip, Y. T. (2005) Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo. Development 132, 3419-3429 https://doi.org/10.1242/dev.01903
  84. Gordon, M. D., Dionne, M. S., Schneider, D. S. and Nusse, R. (2005) WntD is a feedback inhibitor of Dorsal/NF-${\kappa}$B in Drosophila development and immunity. Nature 437, 746-749 https://doi.org/10.1038/nature04073
  85. Park, J. M., Brady, H., Ruocco, M. G., Sun, H., Williams, D., Lee, S. J., Kato, T., Jr., Richards, N., Chan, K., Mercurio, F., Karin, M. and Wasserman, S. A. (2004) Targeting of TAK1 by the NF-${\kappa}$B protein Relish regulates the JNK-mediated immune response in Drosophila. Genes Dev. 18, 584-594 https://doi.org/10.1101/gad.1168104
  86. Tsuda, M., Seong, K. H. and Aigaki, T. (2006) POSH, a scaffold protein for JNK signaling, binds to ALG-2 and ALIX in Drosophila. FEBS. Lett. 580, 3296-3300 https://doi.org/10.1016/j.febslet.2006.05.005
  87. Foley, E. and O'Farrell, P. H. (2004) Functional dissection of an innate immune response by a genome-wide RNAi screen. PLoS. Biology. 2, E203 https://doi.org/10.1371/journal.pbio.0020203
  88. Chu, K., Niu, X. and Williams, L. T. (1995) A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc. Natl. Acad. Sci. U.S.A. 92, 11894-11898. https://doi.org/10.1073/pnas.92.25.11894
  89. Park, M. Y., Jang, H. D., Lee, S. Y., Lee, K. J. and Kim, E. (2004) Fas-associated factor-1 inhibits nuclear factor-${\kappa}$B (NF-${\kappa}$B) activity by interfering with nuclear translocation of the RelA (p65) subunit of NF-${\kappa}$B. J. Biol. Chem. 279, 2544-2549 https://doi.org/10.1074/jbc.M304565200
  90. Ryu, S. W., Lee, S. J., Park, M. Y., Jun, J. I., Jung, Y. K. and Kim, E. (2003) Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex. J. Biol. Chem. 278, 24003-24010 https://doi.org/10.1074/jbc.M302200200
  91. Kim, M., Lee, J. H., Lee, S. Y., Kim, E. and Chung, J. (2006) Caspar, a suppressor of antibacterial Immunity in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 103, 16358-16363. https://doi.org/10.1073/pnas.0603238103
  92. Khush, R. S., Cornwell, W. D., Uram, J. N. and Lemaitre, B. (2002) A ubiquitin-proteasome pathway represses the Drosophila immune deficiency signaling cascade. Curr. Biol. 12, 1728-1737 https://doi.org/10.1016/S0960-9822(02)01214-9
  93. Davis, R. J. (1999) Signal transduction by the c-Jun N-terminal kinase. Biochemical Society Symposium 64, 1-12
  94. Agaisse, H., Petersen, U. M., Boutros, M., Mathey-Prevot, B. and Perrimon, N. (2003) Signaling role of hemocytes in Drosophila JAK/STAT-dependent response to septic injury. Dev. Cell. 5, 441-450 https://doi.org/10.1016/S1534-5807(03)00244-2
  95. Matova, N. and Anderson, K. V. (2006) Rel/NF-${\kappa}$B double mutants reveal that cellular immunity is central to Drosophila host defense. Proc. Natl. Acad. Sci. U.S.A. 103, 16424-16429. https://doi.org/10.1073/pnas.0605721103
  96. Cox, C. R. and Gilmore, M. S. (2007) Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis. Infect. Immun. 75, 1565-1576 https://doi.org/10.1128/IAI.01496-06
  97. Ren, C., Webster, P., Finkel, S. E. and Tower, J. (2007) Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell. Metabolism. 6, 144-152 https://doi.org/10.1016/j.cmet.2007.06.006
  98. Ryu, J. H., Kim, S. H., Lee, H. Y., Bai, J. Y., Nam, Y. D., Bae, J. W., Lee, D. G., Shin, S. C., Ha, E. M. and Lee, W. J. (2008) Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319, 777-782 https://doi.org/10.1126/science.1149357
  99. Lengyel, J. A. and Iwaki, D. D. (2002) It takes guts: the Drosophila hindgut as a model system for organogenesis. Dev. Biol. 243, 1-19 https://doi.org/10.1006/dbio.2002.0577
  100. Sodergren, E., Weinstock, G. M., Davidson, E. H., Cameron, R. A., Gibbs, R. A., Angerer, R. C., Angerer, L. M., Arnone, M. I., Burgess, D. R., Burke, R. D., Coffman, J. A., Dean, M., Elphick, M. R., Ettensohn, C. A., Foltz, K. R., Hamdoun, A., Hynes, R. O., Klein, W. H., Marzluff, W., McClay, D. R., Morris, R. L., Mushegian, A., Rast, J. P., Smith, L. C., Thorndyke, M. C., Vacquier, V. D., Wessel, G. M., Wray, G., Zhang, L., Elsik, C. G., Ermolaeva, O., Hlavina, W., Hofmann, G., Kitts, P., Landrum, M. J., Mackey, A. J., Maglott, D., Panopoulou, G., Poustka, A. J., Pruitt, K., Sapojnikov, V., Song, X., Souvorov, A., Solovyev, V., Wei, Z., Whittaker, C. A., Worley, K., Durbin, K. J., Shen, Y., Fedrigo, O., Garfield, D., Haygood, R., Primus, A., Satija, R., Severson, T., Gonzalez-Garay, M. L., Jackson, A. R., Milosavljevic, A., Tong, M., Killian, C. E., Livingston, B. T., Wilt, F. H., Adams, N., Belle, R., Carbonneau, S., Cheung, R., Cormier, P., Cosson, B., Croce, J., Fernandez- Guerra, A., Geneviere, A. M., Goel, M., Kelkar, H., Morales, J., Mulner-Lorillon, O., Robertson, A. J., Goldstone, J. V., Cole, B., Epel, D., Gold, B., Hahn, M. E., Howard-Ashby, M., Scally, M., Stegeman, J. J., Allgood, E. L., Cool, J., Judkins, K. M., McCafferty, S. S., Musante, A. M., Obar, R. A., Rawson, A. P., Rossetti, B. J., Gibbons, I. R., Hoffman, M. P., Leone, A., Istrail, S., Materna, S. C., Samanta, M. P., Stolc, V., Tongprasit, W., Tu, Q., Bergeron, K. F., Brandhorst, B. P., Whittle, J., Berney, K., Bottjer, D. J., Calestani, C., Peterson, K., Chow, E., Yuan, Q. A., Elhaik, E., Graur, D., Reese, J. T., Bosdet, I., Heesun, S., Marra, M. A., Schein, J. anderson, M. K., Brockton, V., Buckley, K. M., Cohen, A. H., Fugmann, S. D., Hibino, T., Loza-Coll, M., Majeske, A. J., Messier, C., Nair, S. V., Pancer, Z., Terwilliger, D. P., Agca, C., Arboleda, E., Chen, N., Churcher, A. M., Hallbook, F., Humphrey, G. W., Idris, M. M., Kiyama, T., Liang, S., Mellott, D., Mu, X., Murray, G., Olinski, R. P., Raible, F., Rowe, M., Taylor, J. S., Tessmar-Raible, K., Wang, D., Wilson, K. H., Yaguchi, S., Gaasterland, T., Galindo, B. E., Gunaratne, H. J., Juliano, C., Kinukawa, M., Moy, G. W., Neill, A. T., Nomura, M., Raisch, M., Reade, A., Roux, M. M., Song, J. L., Su, Y. H., Townley, I. K., Voronina, E., Wong, J. L., Amore, G., Branno, M., Brown, E. R., Cavalieri, V., Duboc, V., Duloquin, L., Flytzanis, C., Gache, C., Lapraz, F., Lepage, T., Locascio, A., Martinez, P., Matassi, G., Matranga, V., Range, R., Rizzo, F., Rottinger, E., Beane, W., Bradham, C., Byrum, C., Glenn, T., Hussain, S., Manning, G., Miranda, E., Thomason, R., Walton, K., Wikramanayke, A., Wu, S. Y., Xu, R., Brown, C. T., Chen, L., Gray, R. F., Lee, P. Y., Nam, J., Oliveri, P., Smith, J., Muzny, D., Bell, S., Chacko, J., Cree, A., Curry, S., Davis, C., Dinh, H., Dugan-Rocha, S., Fowler, J., Gill, R., Hamilton, C., Hernandez, J., Hines, S., Hume, J., Jackson, L., Jolivet, A., Kovar, C., Lee, S., Lewis, L., Miner, G., Morgan, M., Nazareth, L. V., Okwuonu, G., Parker, D., Pu, L. L., Thorn, R. and Wright, R. (2006) The genome of the sea urchin Strongylocentrotus purpuratus. Science 314, 941-952 https://doi.org/10.1126/science.1133609
  101. Flatt, T., Tu, M. P. and Tatar, M. (2005) Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays 27, 999-1010 https://doi.org/10.1002/bies.20290
  102. Zerofsky, M., Harel, E., Silverman, N. and Tatar, M. (2005) Aging of the innate immune response in Drosophila melanogaster. Aging Cell 4, 103-108 https://doi.org/10.1111/j.1474-9728.2005.00147.x

Cited by

  1. Reciprocal Analysis of Francisella novicida Infections of a Drosophila melanogaster Model Reveal Host-Pathogen Conflicts Mediated by Reactive Oxygen and imd-Regulated Innate Immune Response vol.6, pp.8, 2010, https://doi.org/10.1371/journal.ppat.1001065
  2. Comparative RNA-sequencing analysis of mthl1 functions and signal transductions in Tribolium castaneum vol.547, pp.2, 2014, https://doi.org/10.1016/j.gene.2014.06.064
  3. Longevity-modulating effects of symbiosis: insights from Drosophila–Wolbachia interaction vol.17, pp.5-6, 2016, https://doi.org/10.1007/s10522-016-9653-9
  4. Immune-Related Transcriptome of Coptotermes formosanus Shiraki Workers: The Defense Mechanism vol.8, pp.7, 2013, https://doi.org/10.1371/journal.pone.0069543
  5. Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections vol.6, pp.3, 2011, https://doi.org/10.1371/journal.pone.0014743
  6. Shotgun proteomic analysis of the fat body during metamorphosis of domesticated silkworm (Bombyx mori) vol.38, pp.5, 2010, https://doi.org/10.1007/s00726-009-0342-8
  7. Immunity Without Antibodies… vol.-1, pp.-1, 2009, https://doi.org/10.2478/v10052-009-0003-9
  8. Gut-microbiota interactions in non-mammals: What can we learn from Drosophila? vol.24, pp.1, 2012, https://doi.org/10.1016/j.smim.2011.11.003
  9. Signaling pathways regulating innate immune responses in shrimp vol.34, pp.4, 2013, https://doi.org/10.1016/j.fsi.2012.08.023
  10. Post-transcriptional Regulation of Genes Encoding Anti-microbial Peptides inDrosophila vol.284, pp.13, 2009, https://doi.org/10.1074/jbc.M806778200
  11. Functional genomics of the evolution of increased resistance to parasitism in Drosophila vol.20, pp.5, 2011, https://doi.org/10.1111/j.1365-294X.2010.04911.x
  12. Insect cytokine paralytic peptide activates innate immunity via nitric oxide production in the silkworm Bombyx mori vol.39, pp.3, 2013, https://doi.org/10.1016/j.dci.2012.10.014
  13. RNAi knock-down of the Litopenaeus vannamei Toll gene (LvToll) significantly increases mortality and reduces bacterial clearance after challenge with Vibrio harveyi vol.34, pp.1, 2010, https://doi.org/10.1016/j.dci.2009.08.003
  14. Scrutinizing the immune defence inventory of Camponotus floridanus applying total transcriptome sequencing vol.16, pp.1, 2015, https://doi.org/10.1186/s12864-015-1748-1
  15. Genome-Wide Analysis of Host Responses to Four Different Types of Microorganisms inBombyx Mori(Lepidoptera: Bombycidae) vol.16, pp.1, 2016, https://doi.org/10.1093/jisesa/iew020
  16. Deletion of Shp2 in bronchial epithelial cells impairs IL-25 production in vitro, but has minor influence on asthmatic inflammation in vivo vol.12, pp.5, 2017, https://doi.org/10.1371/journal.pone.0177334
  17. Virus and dsRNA-triggered transcriptional responses reveal key components of honey bee antiviral defense vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-06623-z
  18. Heterodimers of NF- B transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila vol.107, pp.33, 2010, https://doi.org/10.1073/pnas.1009473107
  19. A new role for T cells in dampening innate inflammatory responses vol.53, pp.2, 2010, https://doi.org/10.1007/s11427-010-0040-5
  20. Immune homeostasis to microorganisms in the guts of triatomines (Reduviidae): a review vol.105, pp.5, 2010, https://doi.org/10.1590/S0074-02762010000500001
  21. Transcriptomic profiling of Microplitis demolitor bracovirus reveals host, tissue and stage-specific patterns of activity vol.92, pp.9, 2011, https://doi.org/10.1099/vir.0.032680-0
  22. Some latest achievements in immunology research vol.56, pp.35, 2011, https://doi.org/10.1007/s11434-011-4854-8
  23. A Fas associated factor negatively regulates anti-bacterial immunity by promoting Relish degradation in Bombyx mori vol.63, 2015, https://doi.org/10.1016/j.ibmb.2015.06.009
  24. Patterns of Pathogenesis: Discrimination of Pathogenic and Nonpathogenic Microbes by the Innate Immune System vol.6, pp.1, 2009, https://doi.org/10.1016/j.chom.2009.06.007
  25. DrosophilaRas/MAPK signalling regulates innate immune responses in immune and intestinal stem cells vol.30, pp.6, 2011, https://doi.org/10.1038/emboj.2011.4
  26. The initial analysis of a serine proteinase gene (AccSp10) from Apis cerana cerana: possible involvement in pupal development, innate immunity and abiotic stress responses 2017, https://doi.org/10.1007/s12192-017-0818-5
  27. miR-34 Modulates Innate Immunity and Ecdysone Signaling in Drosophila vol.12, pp.11, 2016, https://doi.org/10.1371/journal.ppat.1006034
  28. dRYBP Contributes to the Negative Regulation of the Drosophila Imd Pathway vol.8, pp.4, 2013, https://doi.org/10.1371/journal.pone.0062052
  29. Wolbachia Infection Decreased the Resistance of Drosophila to Lead vol.7, pp.3, 2012, https://doi.org/10.1371/journal.pone.0032643
  30. Annotation of the Asian Citrus Psyllid Genome Reveals a Reduced Innate Immune System vol.7, 2016, https://doi.org/10.3389/fphys.2016.00570
  31. Innate Immune Signaling Pathways in Animals: Beyond Reductionism vol.28, pp.3-4, 2009, https://doi.org/10.1080/08830180902839777
  32. Immune signaling pathways activated in response to different pathogenic micro-organisms in Bombyx mori vol.65, pp.2, 2015, https://doi.org/10.1016/j.molimm.2015.02.018
  33. Mosquito immune defenses against Plasmodium infection vol.34, pp.4, 2010, https://doi.org/10.1016/j.dci.2009.12.005
  34. The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes vol.8, 2017, https://doi.org/10.3389/fmicb.2017.01421
  35. Gene discovery and differential expression analysis of humoral immune response elements in female Culicoides sonorensis (Diptera: Ceratopogonidae) vol.7, pp.1, 2014, https://doi.org/10.1186/1756-3305-7-388
  36. Drosophila Intestinal Response to Bacterial Infection: Activation of Host Defense and Stem Cell Proliferation vol.5, pp.2, 2009, https://doi.org/10.1016/j.chom.2009.01.003
  37. A different repertoire of Galleria mellonella antimicrobial peptides in larvae challenged with bacteria and fungi vol.34, pp.10, 2010, https://doi.org/10.1016/j.dci.2010.06.005
  38. Temporal waves of coherent gene expression during Drosophila embryogenesis vol.26, pp.21, 2010, https://doi.org/10.1093/bioinformatics/btq513
  39. Evolutionary rate patterns of genes involved in the Drosophila Toll and Imd signaling pathway vol.13, pp.1, 2013, https://doi.org/10.1186/1471-2148-13-245
  40. Insect Cytokine Paralytic Peptide (PP) Induces Cellular and Humoral Immune Responses in the SilkwormBombyx mori vol.285, pp.37, 2010, https://doi.org/10.1074/jbc.M110.138446
  41. A Shared Role for RBF1 and dCAP-D3 in the Regulation of Transcription with Consequences for Innate Immunity vol.8, pp.4, 2012, https://doi.org/10.1371/journal.pgen.1002618
  42. Identification of immune response-related genes in the Chinese oak silkworm, Antheraea pernyi by suppression subtractive hybridization vol.114, pp.3, 2013, https://doi.org/10.1016/j.jip.2013.09.004
  43. The Shrimp NF-κB Pathway Is Activated by White Spot Syndrome Virus (WSSV) 449 to Facilitate the Expression of WSSV069 (ie1), WSSV303 and WSSV371 vol.6, pp.9, 2011, https://doi.org/10.1371/journal.pone.0024773
  44. A Toll-Spätzle pathway in the tobacco hornworm, Manduca sexta vol.42, pp.7, 2012, https://doi.org/10.1016/j.ibmb.2012.03.009
  45. Switching between humoral and cellular immune responses in Drosophila is guided by the cytokine GBP vol.5, 2014, https://doi.org/10.1038/ncomms5628
  46. Prochloraz and coumaphos induce different gene expression patterns in three developmental stages of the Carniolan honey bee (Apis mellifera carnica Pollmann) vol.128, 2016, https://doi.org/10.1016/j.pestbp.2015.09.015
  47. Long-Range Activation of Systemic Immunity through Peptidoglycan Diffusion in Drosophila vol.5, pp.12, 2009, https://doi.org/10.1371/journal.ppat.1000694
  48. Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster vol.68, pp.22, 2011, https://doi.org/10.1007/s00018-011-0828-x
  49. Functional analysis of Grp and Iris, the gag and env domesticated errantivirus genes, in the Drosophila melanogaster genome vol.50, pp.3, 2016, https://doi.org/10.1134/S0026893316020151
  50. The sandfly Lutzomyia longipalpis LL5 embryonic cell line has active Toll and Imd pathways and shows immune responses to bacteria, yeast and Leishmania vol.9, pp.1, 2016, https://doi.org/10.1186/s13071-016-1507-4
  51. Modulation of epithelial innate immunity by autocrine production of nitric oxide vol.162, pp.1, 2009, https://doi.org/10.1016/j.ygcen.2008.09.012
  52. Molecular cloning and characterization of a short peptidoglycan recognition protein (PGRP-S) with antibacterial activity from the bumblebee Bombus ignitus vol.34, pp.9, 2010, https://doi.org/10.1016/j.dci.2010.04.007
  53. Toll pathway modulates TNF-induced JNK-dependent cell death inDrosophila vol.5, pp.7, 2015, https://doi.org/10.1098/rsob.140171
  54. Integrated Immune and Cardiovascular Function in Pancrustacea: Lessons from the Insects vol.55, pp.5, 2015, https://doi.org/10.1093/icb/icv021
  55. Caudal is a negative regulator of the Anopheles IMD Pathway that controls resistance to Plasmodium falciparum infection vol.39, pp.4, 2013, https://doi.org/10.1016/j.dci.2012.10.009
  56. Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-00118-7
  57. Bacteria sensing mechanisms in Drosophila gut: Local and systemic consequences vol.64, 2016, https://doi.org/10.1016/j.dci.2016.01.001
  58. Do adaptive immune cells suppress or activate innate immunity? vol.30, pp.1, 2009, https://doi.org/10.1016/j.it.2008.10.003
  59. Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: Key regulators of innate immunity vol.124, pp.2, 2009, https://doi.org/10.1016/j.pharmthera.2009.06.012
  60. From pathogens to microbiota: How Drosophila intestinal stem cells react to gut microbes vol.64, 2016, https://doi.org/10.1016/j.dci.2016.02.008
  61. Bacterial challenge initiates endosome-lysosome response inDrosophilaimmune tissues vol.2, pp.1, 2013, https://doi.org/10.4161/intv.23889
  62. On-bead tryptic proteolysis: An attractive procedure for LC-MS/MS analysis of the Drosophila caspase 8 protein complex during immune response against bacteria vol.75, pp.15, 2012, https://doi.org/10.1016/j.jprot.2012.03.003
  63. Morphological and Molecular Characterization of Adult Midgut Compartmentalization in Drosophila vol.3, pp.5, 2013, https://doi.org/10.1016/j.celrep.2013.04.001
  64. Identification of Immunity-Related Genes in Ostrinia furnacalis against Entomopathogenic Fungi by RNA-Seq Analysis vol.9, pp.1, 2014, https://doi.org/10.1371/journal.pone.0086436
  65. Comparative genomics allows the discovery of cis-regulatory elements in mosquitoes vol.106, pp.9, 2009, https://doi.org/10.1073/pnas.0813264106
  66. Comparison of the humoral and cellular immune responses between body and head lice following bacterial challenge vol.41, pp.5, 2011, https://doi.org/10.1016/j.ibmb.2011.01.011
  67. Molecular Mechanisms of Aging and Immune System Regulation in Drosophila vol.13, pp.12, 2012, https://doi.org/10.3390/ijms13089826
  68. Gut homeostasis in a microbial world: insights from Drosophila melanogaster vol.11, pp.9, 2013, https://doi.org/10.1038/nrmicro3074
  69. Functional Analysis of PGRP-LA in Drosophila Immunity vol.8, pp.7, 2013, https://doi.org/10.1371/journal.pone.0069742
  70. Insect immunology and hematopoiesis vol.58, 2016, https://doi.org/10.1016/j.dci.2015.12.006
  71. Overview on the recent study of antimicrobial peptides: Origins, functions, relative mechanisms and application vol.37, pp.2, 2012, https://doi.org/10.1016/j.peptides.2012.07.001
  72. Modulation of the transcriptional response of innate immune and RNAi genes upon exposure to dsRNA and LPS in silkmoth-derived Bm5 cells overexpressing BmToll9-1 receptor vol.66, 2014, https://doi.org/10.1016/j.jinsphys.2014.05.008
  73. Drosophila miR-964 modulates Toll signaling pathway in response to bacterial infection vol.77, 2017, https://doi.org/10.1016/j.dci.2017.08.008
  74. unpaired (upd)-3 expression and other immune-related functions are stimulated by interleukin-8 in Drosophila melanogaster SL2 cell line vol.44, pp.2, 2008, https://doi.org/10.1016/j.cyto.2008.08.011
  75. Mosquito Immunity against Arboviruses vol.6, pp.11, 2014, https://doi.org/10.3390/v6114479
  76. Drosophilablood cells and their role in immune responses vol.282, pp.8, 2015, https://doi.org/10.1111/febs.13235
  77. Effect of Varroa destructor, Wounding and Varroa Homogenate on Gene Expression in Brood and Adult Honey Bees vol.12, pp.1, 2017, https://doi.org/10.1371/journal.pone.0169669
  78. Heixuedian (heix), a potential melanotic tumor suppressor gene, exhibits specific spatial and temporal expression pattern during drosophila hematopoiesis vol.398, pp.2, 2015, https://doi.org/10.1016/j.ydbio.2014.12.001
  79. Survival and immune-related gene expression in Litopenaeus vannamei co-infected with WSSV and Vibrio parahaemolyticus vol.464, 2016, https://doi.org/10.1016/j.aquaculture.2016.08.024
  80. Misexpression screen delineates novel genes controlling Drosophila lifespan vol.133, pp.5, 2012, https://doi.org/10.1016/j.mad.2012.02.001
  81. Fas-associated factor 1plays a negative regulatory role in the antibacterial immunity ofLocusta migratoria vol.22, pp.4, 2013, https://doi.org/10.1111/imb.12029
  82. Effects of transient high temperature treatment on the intestinal flora of the silkworm Bombyx mori vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-03565-4
  83. The N-terminal half of the Drosophila Rel/NF-κB factor Relish, REL-68, constitutively activates transcription of specific Relish target genes vol.33, pp.5, 2009, https://doi.org/10.1016/j.dci.2008.12.002
  84. Antimicrobial peptides: therapeutic potentials vol.12, pp.12, 2014, https://doi.org/10.1586/14787210.2014.976613
  85. Nematobacterial Complexes and Insect Hosts: Different Weapons for the Same War vol.9, pp.3, 2018, https://doi.org/10.3390/insects9030117
  86. Unraveling the Molecular Mechanism of Immunosenescence in Drosophila vol.19, pp.9, 2018, https://doi.org/10.3390/ijms19092472
  87. Role of Glial Immunity in Lifespan Determination: A Drosophila Perspective vol.9, pp.1664-3224, 2018, https://doi.org/10.3389/fimmu.2018.01362
  88. RIOK-1 Is a Suppressor of the p38 MAPK Innate Immune Pathway in Caenorhabditis elegans vol.9, pp.1664-3224, 2018, https://doi.org/10.3389/fimmu.2018.00774
  89. vol.197, pp.2, 2014, https://doi.org/10.1534/genetics.113.160937