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Overview of Innate Immunity in Drosophila

  • Published : 2005.03.31
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Abstract

Drosophila protects itself from infection by microbial organisms by means of its pivotal defense, the so-called innate immunity system. This is its sole defense as it lacks an adaptive immunity system such as is found in mammals. The strong conservation of innate immunity systems in organisms from Drosophila to mammals, and the ease with which Drosophila can be manipulated genetically, makes this fly a good model system for investigating the mechanisms of virulence of a number of medically important pathogens. Potentially damaging endogenous and/or exogenous challenges sensed by specific receptors initiate signals via the Toll and/or Imd signaling pathways. These in turn activate the transcription factors Dorsal, Dorsal-related immune factor (Dif) and Relish, culminating in transcription of genes involved in the production of antimicrobial peptides, melanization, phagocytosis, and the cytoskeletal rearrangement required for appropriate responses. Clarifying the regulatory interactions between the various pathways involved is very important for understanding the specificity and termination mechanism of the immune response.

Keywords

References

  1. 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
  2. Alonzi, T., Maritano, D., Gorgoni, B., Rizzuto, G., Libert, C. and Poli, V. (2001) Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene inactivation [correction of activation] in the liver. Mol. Cell. Biol. 21, 1621-1632. https://doi.org/10.1128/MCB.21.5.1621-1632.2001
  3. Baumann, H. and Gauldie, J. (1994) The acute phase response. Immunol. Today 15, 74-80 https://doi.org/10.1016/0167-5699(94)90137-6
  4. Belvin, M. P. and Anderson, K. V. (1996) A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu. Rev. Cell Dev. BioI. 12, 393-416 https://doi.org/10.1146/annurev.cellbio.12.1.393
  5. 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
  6. Braun, A., Hoffmann, J. A. and Meister, M. (1998) Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes. Proc. Natl. Acad. Sci. USA 95, 14337-14342 https://doi.org/10.1073/pnas.95.24.14337
  7. 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
  8. Bulet, P., Hctru, C, Dimarcq, J. L. and Hoffmann, D. (1999) Antimicrobial peptides in insects; structnre and function. Dev. Compo Immunol. 23, 329-344 https://doi.org/10.1016/S0145-305X(99)00015-4
  9. Chang, L. and Karin, M. (2001) Mammalian MAP kinase signaling cascades. Nature 410, 37-40 https://doi.org/10.1038/35065000
  10. Choe, K. M., Werner, T., Stoven, 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
  11. De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D. U., Jin, R., Jones, J., Cong, R. and Franzoso, G. (2001) Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signaling. Nature 414, 308-313 https://doi.org/10.1038/35104560
  12. Engstrom, Y., Kadalayil, L., Sun, S. C, Samakovlis, C., Hultmark, D. and Faye, I. (1993) kappa B-like motifs regulate the induction of immune genes in Drosophila. J. Mol. Biol. 232, 327-333 https://doi.org/10.1006/jmbi.1993.1392
  13. Ferrandon, D., Jung, A. C, Criqui, M., Lemaitre, B., UttenweilerJoseph, S., Michaut, L., Reichhart, J. and Hoffmann, J. A. (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 https://doi.org/10.1093/emboj/17.5.1217
  14. Fossett, N., Tevosian, S. G., Gajewski, K, Zhang, Q., Orkin, S. H. and Schulz, R. A. (2001) The Friend of GATA proteins Ushaped, FOG-I, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila. Proc. Natl. Acad. Sci. USA 98, 7342-7347 https://doi.org/10.1073/pnas.131215798
  15. Franc, N. C, Heitzler, P., Ezekowitz, R. A. and White, K (1999) Requirement for croquemort in phagocytosis of apoptotic cells in Drosophila. Science 284, 1991-1994 https://doi.org/10.1126/science.284.5422.1991
  16. 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
  17. Glise, B., Bourbon, H. and Noselli, S. (1995) hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial cell sheet movement. Cell 83, 451-461 https://doi.org/10.1016/0092-8674(95)90123-X
  18. Goberdhan, D. C. and Wilson, C. (1998) JNK, cytoskeletal regulator and stress response kinase? A Drosophila perspective. Bioessays 20, 1009-1019 https://doi.org/10.1002/(SICI)1521-1878(199812)20:12<1009::AID-BIES7>3.0.CO;2-D
  19. 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
  20. Hartenstein, V. and Jan, Y. N. (1992) Stndying Drosophila embryogenesis with P-lacZ enhancer trap lines. Rouxs Arch.Dev. BioI. 201, 194-220 https://doi.org/10.1007/BF00188752
  21. Hibi, M., Lin, A, Smeal, T., Minden, A. and Karin, M. (1993) Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7, 2135-2148 https://doi.org/10.1101/gad.7.11.2135
  22. Hoffmann, J. A. (2003) The immune response of Drosophila. Nature 426, 33-38 https://doi.org/10.1038/nature02021
  23. Hoffmann, J. A and Reichhart, J. M. (2002) Drosophila innate immunity: an evolutionary perspective. Nature Immunol. 3, 121-126 https://doi.org/10.1038/ni0202-121
  24. Hu, S. and Yang, X. (2000) dFADD, a novel death domaincontaining adapter protein for the Drosophila caspase DREDD. J. Biol. Chem. 275, 30761-30764 https://doi.org/10.1074/jbc.C000341200
  25. Hultmark, D. (2003) Drosophila immunity: paths and patterns. Curr. Opin. Immunol. 15, 12-19 https://doi.org/10.1016/S0952-7915(02)00005-5
  26. Imler, J. L. and Hoffmann, J. A. (2002) Toll receptors in Drosophila: a family of molecules regulating development and immunity. Curr. Top Microbiol. Immunol. 270, 63-79
  27. Ip, Y. T., Reach, M., Engstrom, Y., Kadalayil, L., Cai, H., Gonzalez-Crespo, S., Tatei, K. and Levine, M. (1993) Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell 75, 753-763 https://doi.org/10.1016/0092-8674(93)90495-C
  28. Janeway, C. A. Jr. (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor Symp. Quant. Biol. 54, 1-13
  29. Janeway, C. A. Jr. and Medzhitov, R. (2002) Innate immune recognition. Annu. Rev. Immunol. 20, 197-216 https://doi.org/10.1146/annurev.immunol.20.083001.084359
  30. Kang, D., Liu, G., Lundstrom, A, Gelius, E. and Steiner, H. (1998) A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc. Nail. Acad. Sci. USA 95, 10078-10082 https://doi.org/10.1073/pnas.95.1.78
  31. Kappler, C., Meister, M., Lagueux, M., Gateff, E., Hoffmann, J. A. and Reichhart, J. M. (1993) Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteriachallenged Drosophila. EMBO J 12, 1561-1568
  32. 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 API and NF-kappaB signaling modules. Nature Immunol. 6, 211-218 https://doi.org/10.1038/ni1159
  33. Kim, Y. S., Ryu, J. H., Han, S. J., Choi, K. H., Nam, K. B., Jang, I. H., Lemaitre, B., Brey, P. T. and Lee, W. J. (2000) Gramnegative bacteria-binding protein, a pattern recognition receptor for lipopolysaccharide and beta-1,3-glucan that mediates the signaling for the induction of innate immune genes in Drosophila melanogaster cells. J Biol. Chem. 275, 32721-32727 https://doi.org/10.1074/jbc.M003934200
  34. Kimbrell, D. A. and Beutler, B. (2001) The evolution and genetics of innate immunity. Nat. Rev. Genet. 2, 256-267 https://doi.org/10.1038/35066006
  35. Lagueux, M., Perrodou, E., Levashina, E. A, Capovilla, M. and Hoffmann, J. A. (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 https://doi.org/10.1073/pnas.97.21.11427
  36. Lanot, R., Zachary, D., Holder, F. and Meister, M. (2001) Postembryonic hematopoiesis in Drosophila. Dev. Biol. 230, 243-257 https://doi.org/10.1006/dbio.2000.0123
  37. Lebestky, T., Chang, T., Hartenstein, V. and Banerjee, U. (2000) Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288, 146-149 https://doi.org/10.1126/science.288.5463.146
  38. Lee, W. J., Lee, J. D., Kravchenko, V. V., Ulevitch, R. J. and Brey, P. T. (1996) Purification and molecular cloning of an inducible gram-negative bacteria-binding protein from the silkworm, Bombyx mori. Proc. Nail. Acad. Sci. USA 93, 7888-7893 https://doi.org/10.1073/pnas.93.15.7888
  39. Lemaitre, B., Kromer-Metzger, E., Michaut, L., Nicolas, E., Meister, M., Georgel, P., Reichhart, J. M., and Hoffmann, J. A (1995) A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense. Proc. NatI. Acad. Sci. USA 92, 9465-9469 https://doi.org/10.1073/pnas.92.21.9465
  40. 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
  41. 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. Nature Immunol. 4, 478-484 https://doi.org/10.1038/ni922
  42. Leulier, F., Vidal, S., Saigo, K, Ueda, R. and Lemaitre, B. (2002) Inducible expression of double-stranded RNA reveals a role for dFADD in the regnlation of the antibacterial response in Drosophila adults. Curr. Biol. 12, 996-1000 https://doi.org/10.1016/S0960-9822(02)00873-4
  43. 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
  44. Lin, A. (2003) Activation of the JNK signaling pathway: breaking the brake on apoptosis. Bioessays 25, 17-24 https://doi.org/10.1002/bies.10204
  45. Lu, Y., Wu, L. P. and Anderson, K. V. (2001) The antibacterial arm of the drosophila innate immune response requires an IkappaB kinase. Genes Dev. 15, 104-110. https://doi.org/10.1101/gad.856901
  46. Medzhitov, R. and Janeway, C. Jr. (2000) Innate immunity. N. EngI. J. Med. 343, 338-344 https://doi.org/10.1056/NEJM200008033430506
  47. Meister, M., Hctru, C. and Hoffmann, J. A. (2000) The antimicrobial host defense of Drosophila. Curr. Top. Microbiol. Immunol. 248, 17-36
  48. Meng, X, Khanuja, B.S. and Ip, Y.T. (1999) Toll receptormediated Drosophila immune response requires Dif, an NFkappaB factor. Genes Dev. 13, 792-797 https://doi.org/10.1101/gad.13.7.792
  49. 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
  50. Morisato, D. and Anderson, K. V. (1995) Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo. Annu. Rev. Genet. 29, 371-399 https://doi.org/10.1146/annurev.genet.29.1.371
  51. Nicolas, E., Reichhart, J. M., Hoffmann, J. A. and Lemaitre, B. (1998) In vivo regnlation of the IkappaB homologne cactus during the immune response of Drosophila. J. Biol. Chem. 273, 10463-10469 https://doi.org/10.1074/jbc.273.17.10463
  52. ONeill, L. A. and Greene, C. (1998) Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J. Leukoc. Biol. 63, 650-657
  53. Ochiai, M. and Ashida, M. (2000) A pattern-recognition protein for beta-1,3-glucan. The binding domain and the eDNA cloning of beta-1,3-glucan recognition protein from the silkworm, Bombyx mori. J. BioI. Chem. 275, 4995-5002 https://doi.org/10.1074/jbc.275.7.4995
  54. 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 regnlates the JNK-mediated immune response in Drosophila. Genes Dev. 18, 584-594 https://doi.org/10.1101/gad.1168104
  55. Ramet, M., Lanot, R., Zachary, D. and Manfruelli, P. (2002) JNK signaling pathway is required for efficient wound healing in Drosophila. Dev. Biol 241, 145-156 https://doi.org/10.1006/dbio.2001.0502
  56. 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
  57. Rizki, T. M. and Rizki, R. M. (1984) The cellular defense system of Drosophila melanogaster; in Insect Ultrastructure, King, R. C. and Akai, H. H. (eds.), pp. 579-604, Plenum, New York, USA
  58. Rizki, R. M. and Rizki, T. M. (1984) Selective destruction of a host blood cell type by a parasitoid wasp. Proc. Nail. Acad. Sci. USA 81, 6154-6158 https://doi.org/10.1073/pnas.81.19.6154
  59. Rugendorff, A., Younossi-Hartenstein, A. and Hartenstein, V. (1994) Embryonic orgin and differentiation of the Drosophila heart. Rouxs Arch. Dev. Biol 203, 266-280 https://doi.org/10.1007/BF00360522
  60. 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. Nature Immunol. 1, 342-347 https://doi.org/10.1038/79801
  61. Schneider, D. S., Hudson, K. L., Lin, T. Y. and Anderson, K. V. (1991) Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsalventral polarity in the Drosophila embryo. Genes Dev. 5, 797-807 https://doi.org/10.1101/gad.5.5.797
  62. Silverman, N., Zhou, R., Stoven, S., Pandey, N., Hultmark, D. and Maniatis, T. (2000) A Drosophila IkappaB kinase complex required for Relish cleavage and antibacterial immunity. Genes Dev. 14, 2461-247 https://doi.org/10.1101/gad.817800
  63. 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
  64. Soderhall, K and Cerenius, L. (1998) Role of the prophenoloxidase-activating system in invertebrate immunity. Curr. Opin. Immunol. 10, 23-28 https://doi.org/10.1016/S0952-7915(98)80026-5
  65. St. Johnston, D. and Nusslein-Volhard, C. (1992) The origin of pattern and polarity in the Drosophila embryo. Cell 68, 201-219 https://doi.org/10.1016/0092-8674(92)90466-P
  66. Stoven, S., Ando, I., Kadalayil, L., Engstrom, Y. and Hultmark, D. (2000) Activation of the Drosophila NF-kappaB factor Relish by rapid endoproteolytic cleavage. EMBO Rep. 1, 347-352 https://doi.org/10.1093/embo-reports/kvd072
  67. Stoven, 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-kappaB factor Relish. Proc. Natl. Acad. Sci. USA 100, 5991-5996 https://doi.org/10.1073/pnas.1035902100
  68. Stronach, B. E. and Perrimon, N. (1999) Stress signaling in Drosophila. Oncogene 18, 6172-6182 https://doi.org/10.1038/sj.onc.1203125
  69. Takehana, A, Katsuyama, T., Yano, T., Oshima, Y., Takada, H., Aigaki, T. and Kurata, S. (2002) Overexpression of a patternrecognition receptor, peptidoglycan-recognition protein-LE, activates imdJrelish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae. Proc. Natl. Acad. Sci. USA 99, 13705-13710 https://doi.org/10.1073/pnas.212301199
  70. Tang, G., Minemoto, Y., Dibling, B., Purcell, N. H., Li, Z., Karin, M. and Lin, A. (2001) Inhibition of JNK activation through NF-kappaB target genes. Nature 414, 313-317 https://doi.org/10.1038/35104568
  71. 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. Nature immunol. 3, 91-97 https://doi.org/10.1038/ni747
  72. Tepass, U, Fessler, L. I., Aziz, A and Hartenstein, V. (1994) Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development 120, 1829-1837
  73. Tzou, P., De Gregorio, E. and Lemaitre, B. (2002) How Drosophila combats microbial infection: a model to study innate immunity and host-pathogen interactions. Curr. Opin. Microbiol. 5, 102-110 https://doi.org/10.1016/S1369-5274(02)00294-1
  74. Tzou, P., Ohresser, S., Ferrandon, D., Capovilla, M., Reichhart, J. M., Lemaitre, B., Hoffmann, J. A and Imler, J. L. (2000) Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 13, 737-748 https://doi.org/10.1016/S1074-7613(00)00072-8
  75. Ventura, J. J., Kennedy, N. J., Flavell, R. A and Davis, R. J. (2004) JNK regulates autocrine expression of TGF-beta1. Mol. Cell 15, 269-278 https://doi.org/10.1016/j.molcel.2004.06.007
  76. Verheij, M., Bose, R., Lin, X. H., Yao, B., Jarvis, W. D., Grant, S., Birrer, M. J., Szabo, E., Zon, L. I., Kyriakis, J. M., Haimovitz-Friedman, A, Fuks, Z. and Kolesnick, R. N. (1996) Requirement for ceramide-initiated SAPKlJNK signalling in stress-induced apoptosis. Nature 380, 75-79 https://doi.org/10.1038/380075a0
  77. Vidal, S., Khush, R. S., Leulier, F., Tzou, P., Nakamura, M. and Lemaitre, B. (2001) Mutations in the Drosophila dTAKl gene reveal a conserved function for MAPKKKs in the control of rel/NFkappaB-dependent innate immune responses. Genes Dev. 15, 1900-1912 https://doi.org/10.1101/gad.203301
  78. Wasserman, S. A. (1993) A conserved signal transduction pathway regulating the activity of the rel-like proteins dorsal and NFkappa B. Mol. Biol. Cell 4, 767-77l https://doi.org/10.1091/mbc.4.8.767
  79. Wasserman, S. A. (2000) Toll signaling: the enigma variations. Curr. Opin. Genet. Dev. 10, 497-502 https://doi.org/10.1016/S0959-437X(00)00118-0
  80. 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. Nature Immunol. 4, 794-800 https://doi.org/10.1038/ni955
  81. 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. USA 97, 13772-13777 https://doi.org/10.1073/pnas.97.25.13772

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  19. Prominent down-regulation of storage protein genes after bacterial challenge in eri-silkworm,Samia cynthia ricini vol.67, pp.1, 2008, https://doi.org/10.1002/arch.20214
  20. Social management of LPS-induced inflammation in Formica polyctena ants vol.22, pp.6, 2008, https://doi.org/10.1016/j.bbi.2008.01.010
  21. A common theme in extracellular fluids of beetles: extracellular superoxide dismutases crucial for balancing ROS in response to microbial challenge vol.6, pp.1, 2016, https://doi.org/10.1038/srep24082
  22. Toll pathway modulates TNF-induced JNK-dependent cell death inDrosophila vol.5, pp.7, 2015, https://doi.org/10.1098/rsob.140171
  23. Direct interaction of avermectin with epidermal growth factor receptor mediates the penetration resistance inDrosophilalarvae vol.6, pp.4, 2016, https://doi.org/10.1098/rsob.150231
  24. Modulation of social interactions by immune stimulation in honey bee, Apis mellifera, workers vol.6, pp.1, 2008, https://doi.org/10.1186/1741-7007-6-50
  25. Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity vol.8, pp.1, 2010, https://doi.org/10.1186/1479-5876-8-6