The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: From resistance to resilience

Current Opinion in Immunology

Volumn 25, Issue 1, 2013, Pages 59-70

  Ferrandon, Dominique ^a  

^a UNIVERSITÉ DE STRASBOURG   (France)

Author keywords

[No Author keywords available]

Indexed keywords

PEPTIDOGLYCAN RECOGNITION PROTEIN; PEPTIDOGLYCAN RECOGNITION PROTEIN LA; PEPTIDOGLYCAN RECOGNITION PROTEIN LC; PEPTIDOGLYCAN RECOGNITION PROTEIN LE; PEPTIDOGLYCAN RECOGNITION PROTEIN LF; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG;

ASTHMA; DROSOPHILA MELANOGASTER; ENTERITIS; EPIDERMIS; HOST PATHOGEN INTERACTION; HOST RESISTANCE; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOGENESIS; INFLAMMATION; INFLAMMATORY DISEASE; INTERORGAN COMMUNICATION; INTESTINAL STEM CELL; INTESTINE EPITHELIUM; INTESTINE INFECTION; MICROORGANISM; MUCOSAL IMMUNITY; NONHUMAN; PERMEABILITY BARRIER; PROTEIN EXPRESSION; PROTEIN FUNCTION; RESPIRATORY TRACT INFECTION; REVIEW; STEM CELL;

ADULT STEM CELLS; AGING; ANIMALS; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; ENTEROCYTES; HUMANS; IMMUNITY; INTESTINAL MUCOSA; METAGENOME; STEM CELL NICHE; WOUND HEALING;

EID: 84875239266     PISSN: 09527915     EISSN: 18790372     Source Type: Journal    
DOI: 10.1016/j.coi.2012.11.008     Document Type: Review

References (100)

1. Lemaitre B., Nicolas E., Michaut L., Reichhart J.M., Hoffmann J.A. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996, 86:973-983.
2. Ganesan S., Aggarwal K., Paquette N., Silverman N. NF-kappaB/Rel proteins and the humoral immune responses of Drosophila melanogaster. Curr Top Microbiol Immunol 2011, 349:25-60.
3. Ferrandon D., Imler J.L., Hetru C., Hoffmann J.A. The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 2007, 7:862-874.
4. Davis M.M., Engstrom Y. Immune response in the barrier epithelia: lessons from the fruit fly Drosophila melanogaster. J Innate Immun 2012, 4:273-283.
5. Royet J. Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster. Cell Mol Life Sci 2011, 68:3651-3660.
6. Ferrandon D., Jung A.C., Criqui M.C., Lemaitre B., Uttenweiler-Joseph S., Michaut L., Reichhart J.M., Hoffmann J.A. A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J 1998, 17:1217-1227.
7. Tzou P., Ohresser S., Ferrandon D., Capovilla M., Reichhart J.M., Lemaitre B., Hoffmann J.A., Imler J.L. Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 2000, 13:737-748.
8. Onfelt Tingvall T., Roos E., Engstrom Y. The imd gene is required for local Cecropin expression in Drosophila barrier epithelia. EMBO Rep 2001, 2:239-243.
9. Ryu J.H., Nam K.B., Oh C.T., Nam H.J., Kim S.H., Yoon J.H., Seong J.K., Yoo M.A., Jang I.H., Brey P.T., et al. The homeobox gene Caudal regulates constitutive local expression of antimicrobial peptide genes in Drosophila epithelia. Mol Cell Biol 2004, 24:172-185.
10. Junell A., Uvell H., Davis M.M., Edlundh-Rose E., Antonsson A., Pick L., Engstrom Y. The POU transcription factor Drifter/Ventral veinless regulates expression of Drosophila immune defense genes. Mol Cell Biol 2010, 30:3672-3684.
11. Pedron T., Sansonetti P. Commensals, bacterial pathogens and intestinal inflammation: an intriguing menage a trois. Cell Host Microbe 2008, 3:344-347.
12. Razzell W., Wood W., Martin P. Swatting flies: modelling wound healing and inflammation in Drosophila. Dis Model Mech 2011, 4:569-574.
13. Loof T.G., Schmidt O., Herwald H., Theopold U. Coagulation systems of invertebrates and vertebrates and their roles in innate immunity: the same side of two coins?. J Innate Immun 2011, 3:34-40.
14. Eleftherianos I., Revenis C. Role and importance of phenoloxidase in insect hemostasis. J Innate Immun 2011, 3:28-33.
15. Matova N., Anderson K.V. Drosophila Rel proteins are central regulators of a robust, multi-organ immune network. J Cell Sci 2010, 123:627-633.
16. Bou Aoun R., Hetru C., Troxler L., Doucet D., Ferrandon D., Matt N. Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster. J Innate Immun 2011, 3:52-64.
17. Stroschein-Stevenson S.L., Foley E., O'Farrell P.H., Johnson A.D. Identification of Drosophila gene products required for phagocytosis of Candida albicans. PLoS Biol 2006, 4:e4.
18. Wagner C., Isermann K., Roeder T. Infection induces a survival program and local remodeling in the airway epithelium of the fly. FASEB J 2009, 23:2045-2054.
19. Takehana A., Yano T., Mita S., Kotani A., Oshima Y., Kurata S. Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity. EMBO J 2004, 23:4690-4700.
20. Maillet F., Bischoff V., Vignal C., Hoffmann J., Royet J. The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation. Cell Host Microbe 2008, 3:293-303.
21. Wagner C., Isermann K., Fehrenbach H., Roeder T. Molecular architecture of the fruit fly's airway epithelial immune system. BMC Genomics 2008, 9:446.
22. Akhouayri I., Turc C., Royet J., Charroux B. Toll-8/Tollo negatively regulates antimicrobial response in the Drosophila respiratory epithelium. PLoS Pathog 2011, 7:e1002319.
23. Basbous N., Coste F., Leone P., Vincentelli R., Royet J., Kellenberger C., Roussel A. The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway. EMBO Rep 2011, 12:327-333.
24. Wigglesworth V.B. The properties of the lining membrane of the insect tracheal system. Tissue Cell 1990, 22:231-238.
25. Roeder T., Isermann K., Kallsen K., Uliczka K., Wagner C. A Drosophila asthma model-what the fly tells us about inflammatory diseases of the lung. Recent Advances on Model Hosts 2012, Springer Science+business media LLC, New-York. E. Mylonakis (Ed.).
26. Basset A., Khush R.S., Braun A., Gardan L., Boccard F., Hoffmann J.A., Lemaitre B. The phytopathogenic bacteria Erwinia carotovora infects Drosophila and activates an immune response. Proc Natl Acad Sci U S A 2000, 97:3376-3381.
27. Foley E., O'Farrell P.H. Nitric oxide contributes to induction of innate immune responses to Gram-negative bacteria in Drosophila. Genes Dev 2003, 17:115-125.
28. Zaidman-Remy A., Herve M., Poidevin M., Pili-Floury S., Kim M.S., Blanot D., Oh B.H., Ueda R., Mengin-Lecreulx D., Lemaitre B. The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity 2006, 24:463-473.
29. Bischoff V., Vignal C., Duvic B., Boneca I.G., Hoffmann J.A., Royet J. Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. PLoS Pathog 2006, 2:e14.
30. Dijkers P.F., O'Farrell P.H. Drosophila calcineurin promotes induction of innate immune responses. Curr Biol 2007, 17:2087-2093.
31. Lhocine N., Ribeiro P.S., Buchon N., Wepf A., Wilson R., Tenev T., Lemaitre B., Gstaiger M., Meier P., Leulier F. PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host Microbe 2008, 4:147-158.
32. Buchon N., Broderick N.A., Chakrabarti S., Lemaitre B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 2009, 23:2333-2344.
33. Buchon N., Broderick N.A., Kuraishi T., Lemaitre B. Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol 2010, 8:152.
34. Buchon N., Broderick N.A., Poidevin M., Pradervand S., Lemaitre B. Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe 2009, 5:200-211.
35. Ragab A., Buechling T., Gesellchen V., Spirohn K., Boettcher A.L., Boutros M. Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells. EMBO J 2011, 30:1123-1136.
36. Paredes J.C., Welchman D.P., Poidevin M., Lemaitre B. Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection. Immunity 2011, 35:770-779.
37. Zhou F., Rasmussen A., Lee S., Agaisse H. The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment. Dev Biol 2012, (in press).
38. Zaidman-Remy A., Regan J.C., Brandao A.S., Jacinto A. The Drosophila larva as a tool to study gut-associated macrophages: PI3K regulates a discrete hemocyte population at the proventriculus. Dev Comp Immunol 2012, 36:638-647.
39. Wu S.C., Liao C.W., Pan R.L., Juang J.L. Infection-induced intestinal oxidative stress triggers organ-to-organ immunological communication in Drosophila. Cell Host Microbe 2012, 11:410-417.
40. Bosco-Drayon V., Poidevin M., Boneca I.G., Narbonne-Reveau K., Royet J., Charroux B. Peptidoglycan sensing by the receptor PGRP-LE in the Drosophila gut induces immune responses to infectious bacteria and tolerance to microbiota. Cell Host Microbe 2012, 12:153-165.
41. Neyen C., Poidevin M., Roussel A., Lemaitre B. Tissue- and ligand-specific sensing of gram-negative infection in drosophila by PGRP-LC isoforms and PGRP-LE. J Immunol 2012, 189:1886-1897.
42. Chakrabarti S., Liehl P., Buchon N., Lemaitre B. Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut. Cell Host Microbe 2012, 12:60-70.
43. Osman D., Buchon N., Chakrabarti S., Huang Y.T., Su W.C., Poidevin M., Tsai Y.C., Lemaitre B Autocrine and paracrine unpaired signalling regulate intestinal stem cell maintenance and division. J Cell Sci 2012, (in press).
44. Vodovar N., Vinals M., Liehl P., Basset A., Degrouard J., Spellman P., Boccard F., Lemaitre B. Drosophila host defense after oral infection by an entomopathogenic Pseudomonas species. Proc Natl Acad Sci U S A 2005, 102:11414-11419.
45. Liehl P., Blight M., Vodovar N., Boccard F., Lemaitre B. Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLoS Pathog 2006, 2:e56.
46. Jiang H., Grenley M.O., Bravo M.J., Blumhagen R.Z., Edgar B.A. EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 2010, 8:84-95.
47. Jiang H., Patel P.H., Kohlmaier A., Grenley M.O., McEwen D.G., Edgar B.A. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 2009, 137:1343-1355.
48. Chatterjee M., Ip Y.T. Pathogenic stimulation of intestinal stem cell response in Drosophila. J Cell Physiol 2009, 220:664-671.
49. Shaw R.L., Kohlmaier A., Polesello C., Veelken C., Edgar B.A., Tapon N. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 2010, 137:4147-4158.
50. Opota O., Vallet-Gely I., Vincentelli R., Kellenberger C., Iacovache I., Gonzalez M.R., Roussel A., van der Goot F.G., Lemaitre B. Monalysin, a novel β-pore-forming toxin from the Drosophila pathogen Pseudomonas entomophila, contributes to host intestinal damage and lethality. PLoS Pathog 2011, 7:e1002259.
51. Cordero J.B., Stefanatos R.K., Scopelliti A., Vidal M., Sansom O.J. Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila. EMBO J 2012, 31:3901-3917.
52. Bond D., Foley E. Autocrine platelet-derived growth factor-vascular endothelial growth factor receptor-related (Pvr) pathway activity controls intestinal stem cell proliferation in the adult Drosophila midgut. J Biol Chem 2012, 287:27359-27370.
53. Blow N.S., Salomon R.N., Garrity K., Reveillaud I., Kopin A., Jackson F.R., Watnick P.I. Vibrio cholerae infection of Drosophila melanogaster mimics the human disease cholera. PLoS Pathog 2005, 1:e8.
54. Berkey C.D., Blow N., Watnick P.I. Genetic analysis of Drosophila melanogaster susceptibility to intestinal Vibrio cholerae infection. Cell Microbiol 2009, 11:461-474.
55. Kuraishi T., Binggeli O., Opota O., Buchon N., Lemaitre B. Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster. Proc Natl Acad Sci U S A 2011, 108:15966-15971.
56. Purdy A.E., Watnick P.I. Spatially selective colonization of the arthropod intestine through activation of Vibrio cholerae biofilm formation. Proc Natl Acad Sci U S A 2011, 108:19737-19742.
57. Wang Z., Berkey C.D., Watnick P.I. The Drosophila protein mustard tailors the innate immune response activated by the immune deficiency pathway. J Immunol 2012, 188:3993-4000.
58. Glittenberg M.T., Kounatidis I., Christensen D., Kostov M., Kimber S., Roberts I., Ligoxygakis P. Pathogen and host factors are needed to provoke a systemic host response to gastrointestinal infection of Drosophila larvae by Candida albicans. Dis Model Mech 2011, 4:515-525.
59. Cox C.R., Gilmore M.S. Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis. Infect Immun 2007, 75:1565-1576.
60. Ayyaz A., Giammarinaro P., Liegeois S., Lestradet M., Ferrandon D. A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus. Immunobiology 2012, (in press).
61. Nehme N.T., Liegeois S., Kele B., Giammarinaro P., Pradel E., Hoffmann J.A., Ewbank J.J., Ferrandon D. A model of bacterial intestinal infections in Drosophila melanogaster. PLoS Pathog 2007, 3:e173.
62. Cronin S.J., Nehme N.T., Limmer S., Liegeois S., Pospisilik J.A., Schramek D., Leibbrandt A., Simoes Rde M., Gruber S., Puc U., et al. Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection. Science 2009, 325:340-343.
63. Karpowicz P., Perez J., Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 2010, 137:4135-4145.
64. Apidianakis Y., Pitsouli C., Perrimon N., Rahme L. Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc Natl Acad Sci U S A 2009, 106:20883-20888.
65. Limmer S., Haller S., Drenkard E., Lee J., Yu S., Kocks C., Ausubel F.M., Ferrandon D. Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model. Proc Natl Acad Sci U S A 2011, 108:17378-17383.
66. Limmer S., Quintin J., Hetru C., Ferrandon D. Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions. Curr Drug Targets 2011, 12:978-999.
67. Mulcahy H., Sibley C.D., Surette M.G., Lewenza S. Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo. PLoS Pathog 2011, 7:e1002299.
68. Ha E.M., Oh C.T., Bae Y.S., Lee W.J. A direct role for dual oxidase in Drosophila gut immunity. Science 2005, 310:847-850.
69. 2+ pathway in Drosophila gut immunity. Dev Cell 2009, 16:386-397.
70. Ha E.M., Lee K.A., Seo Y.Y., Kim S.H., Lim J.H., Oh B.H., Kim J., Lee W.J. Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in Drosophila gut. Nat Immunol 2009, 10:949-957.
71. Kumar S., Molina-Cruz A., Gupta L., Rodrigues J., Barillas-Mury C. A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae. Science 2010, 327:1644-1648.
72. Hochmuth C.E., Biteau B., Bohmann D., Jasper H. Redox regulation by keap1 and nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 2011, 8:188-199.
73. Hoeven R., McCallum K.C., Cruz M.R., Garsin D.A. Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans. PLoS Pathog 2011, 7:e1002453.
74. Ryu J.H., Ha E.M., Oh C.T., Seol J-H., Brey P., Jin I., Lee D.L., Kim J., Lee D., Lee W.J. An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity. EMBO J 2006, 25:3693-3701.
75. 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., Lee W.J. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 2008, 319:777-782.
76. Kleino A., Myllymaki H., Kallio J., Vanha-aho L.M., Oksanen K., Ulvila J., Hultmark D., Valanne S., Ramet M. Pirk is a negative regulator of the Drosophila Imd pathway. J Immunol 2008, 180:5413-5422.
77. Aggarwal K., Rus F., Vriesema-Magnuson C., Erturk-Hasdemir D., Paquette N., Silverman N. Rudra interrupts receptor signaling complexes to negatively regulate the IMD pathway. PLoS Pathog 2008, 4:e1000120.
78. Ren C., Webster P., Finkel S.E., Tower J. Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell Metab 2007, 6:144-152.
79. Biteau B., Hochmuth C.E., Jasper H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 2008, 3:442-455.
80. Kocks C., Cho J.H., Nehme N., Ulvila J., Pearson A.M., Meister M., Strom C., Conto S.L., Hetru C., Stuart L.M., et al. Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 2005, 123:335-346.
81. Gendrin M., Welchman D.P., Poidevin M., Herve M., Lemaitre B. Long-range activation of systemic immunity through peptidoglycan diffusion in Drosophila. PLoS Pathog 2009, 5:e1000694.
82. Charriere G.M., Ip W.E., Dejardin S., Boyer L., Sokolovska A., Cappillino M.P., Cherayil B.J., Podolsky D.K., Kobayashi K.S., Silverman N., et al. Identification of Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated muramyl dipeptide transporters. J Biol Chem 2010, 285:20147-20154.
83. Amcheslavsky A., Jiang J., Ip Y.T. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 2009, 4:49-61.
84. Biteau B., Hochmuth C.E., Jasper H. Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 2011, 9:402-411.
85. Jiang H., Edgar B.A. Intestinal stem cells in the adult Drosophila midgut. Exp Cell Res 2011, 317:2780-2788.
86. Ren F., Wang B., Yue T., Yun E.Y., Ip Y.T., Jiang J. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci U S A 2010, 107:21064-21069.
87. Staley B.K., Irvine K.D. Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr Biol 2010, 20:1580-1587.
88. Biteau B., Jasper H. EGF signaling regulates the proliferation of intestinal stem cells in Drosophila. Development 2011, 138:1045-1055.
89. Xu N., Wang S.Q., Tan D., Gao Y., Lin G., Xi R. EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev Biol 2011, 354:31-43.
90. Bulet P., Stocklin R. Insect antimicrobial peptides: structures, properties and gene regulation. Protein Pept Lett 2005, 12:3-11.
91. Moribe H., Konakawa R., Koga D., Ushiki T., Nakamura K., Mekada E. Tetraspanin is required for generation of reactive oxygen species by the dual oxidase system in Caenorhabditis elegans. PLoS Genet 2012, 8:e1002957.
92. Biteau B., Karpac J., Supoyo S., Degennaro M., Lehmann R., Jasper H. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet 2010, 6:e1001159.
93. Choi N.H., Lucchetta E., Ohlstein B. Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway. Proc Natl Acad Sci U S A 2011, 108:18702-18707.
94. Gregg T.G., McCrate A., Reveal G., Hall S., Rypstra A.L. Insectivory and social digestion in Drosophila. Biochem Genet 1990, 28:197-207.
95. Murakami R., Shigenaga A., Kawano E., Matsumoto A., Yamaoka I., Tanimura T. Novel tissue units of regional differentiation in the gut epithelium of Drosophila, as revealed by P-element-mediated detection of enhancer. Roux's Arch. Dev. Biol. 1994, 203:243-249.
96. Cognigni P., Bailey A.P., Miguel-Aliaga I. Enteric neurons and systemic signals couple nutritional and reproductive status with intestinal homeostasis. Cell Metab 2011, 13:92-104.
97. O'Brien L.E., Soliman S.S., Li X., Bilder D. Altered modes of stem cell division drive adaptive intestinal growth. Cell 2011, 147:603-614.
98. Broderick N.A., Lemaitre B. Gut-associated microbes of Drosophila melanogaster. Gut Microbes 2012, 3:307-321.
99. Shin S.C., Kim S.H., You H., Kim B., Kim A.C., Lee K.A., Yoon J.H., Ryu J.H., Lee W.J. Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 2011, 334:670-674.
100. Storelli G., Defaye A., Erkosar B., Hols P., Royet J., Leulier F. Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab 2011, 14:403-414.