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Pseudomonas aeruginosa Suppresses Host Immunity by Activating the DAF-2 Insulin-Like Signaling Pathway in Caenorhabditis elegans

DOI: 10.1371/journal.ppat.1000175

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Abstract:

Some pathogens have evolved mechanisms to overcome host immune defenses by inhibiting host defense signaling pathways and suppressing the expression of host defense effectors. We present evidence that Pseudomonas aeruginosa is able to suppress the expression of a subset of immune defense genes in the animal host Caenorhabditis elegans by activating the DAF-2/DAF-16 insulin-like signaling pathway. The DAF-2/DAF-16 pathway is important for the regulation of many aspects of organismal physiology, including metabolism, stress response, longevity, and immune function. We show that intestinal expression of DAF-16 is required for resistance to P. aeruginosa and that the suppression of immune defense genes is dependent on the insulin-like receptor DAF-2 and the FOXO transcription factor DAF-16. By visualizing the subcellular localization of DAF-16::GFP fusion protein in live animals during infection, we show that P. aeruginosa–mediated downregulation of a subset of immune genes is associated with the ability to translocate DAF-16 from the nuclei of intestinal cells. Suppression of DAF-16 is mediated by an insulin-like peptide, INS-7, which functions upstream of DAF-2. Both the inhibition of DAF-16 and downregulation of DAF-16–regulated genes, such as thn-2, lys-7, and spp-1, require the P. aeruginosa two-component response regulator GacA and the quorum-sensing regulators LasR and RhlR and are not observed during infection with Salmonella typhimurium or Enterococcus faecalis. Our results reveal a new mechanism by which P. aeruginosa suppresses host immune defense.

References

[1]  Kaufmann SHE, Medzhitov R, Gordon S (2004) The innate immune response to infection. Washington, D.C.: ASM Press.
[2]  Janeway CA Jr., Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20: 197–216.
[3]  Matzinger P (2002) The danger model: a renewed sense of self. Science 296: 301–305.
[4]  Kopp EB, Medzhitov R (1999) The Toll-receptor family and control of innate immunity. Curr Opin Immunol 11: 13–18.
[5]  Anderson KV (2000) Toll signaling pathways in the innate immune response. Curr Opin Immunol 12: 13–19.
[6]  Pujol N, Link EM, Liu LX, Kurz CL, Alloing G, et al. (2001) A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr Biol 11: 809–821.
[7]  Shapira M, Hamlin BJ, Rong J, Chen K, Ronen M, et al. (2006) A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci U S A 103: 14086–14091.
[8]  Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, et al. (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2: e183. doi: 10.1371/journal.pgen.0020183.
[9]  O'Rourke D, Baban D, Demidova M, Mott R, Hodgkin J (2006) Genomic clusters, putative pathogen recognition molecules, and antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res 16: 1005–1016.
[10]  Mallo GV, Kurz CL, Couillault C, Pujol N, Granjeaud S, et al. (2002) Inducible antibacterial defense system in C. elegans. Curr Biol 12: 1209–1214.
[11]  Ewbank JJ (2006) Signaling in the immune response. WormBook 1–12.
[12]  Gravato-Nobre MJ, Hodgkin J (2005) Caenorhabditis elegans as a model for innate immunity to pathogens. Cell Microbiol 7: 741–751.
[13]  Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, et al. (2002) A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297: 623–626.
[14]  Tan M-W (2001) Genetic and genomic dissection of host-pathogen interactions using a P. aeruginosa-C. elegans pathogenesis model. Pediatric Pulmonol 31: 96–97.
[15]  Garsin DA, Villanueva JM, Begun J, Kim DH, Sifri CD, et al. (2003) Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300: 1921.
[16]  Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature.
[17]  Mochii M, Yoshida S, Morita K, Kohara Y, Ueno N (1999) Identification of transforming growth factor-beta- regulated genes in caenorhabditis elegans by differential hybridization of arrayed cDNAs. Proc Natl Acad Sci U S A 96: 15020–15025.
[18]  Kato Y, Aizawa T, Hoshino H, Kawano K, Nitta K, et al. (2002) abf-1 and abf-2, ASABF-type antimicrobial peptide genes in Caenorhabditis elegans. Biochem J 361: 221–230.
[19]  Banyai L, Patthy L (1998) Amoebapore homologs of Caenorhabditis elegans. Biochim Biophys Acta 1429: 259–264.
[20]  Alegado RA, Tan MW (2008) Resistance to antimicrobial peptides contributes to persistence of Salmonella typhimurium in the C. elegans intestine. Cell Microbiol 10: 1259–1273.
[21]  Wong D, Bazopoulou D, Pujol N, Tavernarakis N, Ewbank JJ (2007) Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection. Genome Biol 8: R194.
[22]  Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, et al. (2004) TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol 5: 488–494.
[23]  Kerry S, TeKippe M, Gaddis NC, Aballay A (2006) GATA transcription factor required for immunity to bacterial and fungal pathogens. PLoS ONE 1: e77. doi: 10.1371/journal.pone.0000077.
[24]  Wood RE (1976) Pseudomonas: the compromised host. Hosp Pract 11: 91–100.
[25]  Saiman L, Siegel J (2004) Infection control in cystic fibrosis. Clin Microbiol Rev 17: 57–71.
[26]  Lyczak JB, Cannon CL, Pier GB (2002) Lung infections associated with cystic fibrosis. Clin Microbiol Rev 15: 194–222.
[27]  Reimmann C, Beyeler M, Latifi A, Winteler H, Foglino M, et al. (1997) The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24: 309–319.
[28]  Rahme LG, Ausubel FM, Cao H, Drenkard E, Goumnerov BC, et al. (2000) Plants and animals share functionally common bacterial virulence factors. Proc Natl Acad Sci U S A 97: 8815–8821.
[29]  Turner JM, Messenger AJ (1986) Occurrence, biochemistry and physiology of phenazine pigment production. Adv Microb Physiol 27: 211–275.
[30]  Lau GW, Hassett DJ, Ran H, Kong F (2004) The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med 10: 599–606.
[31]  Gross GN, Rehm SR, Pierce AK (1978) The effect of complement depletion on lung clearance of bacteria. J Clin Invest 62: 373–378.
[32]  Hong YQ, Ghebrehiwet B (1992) Effect of Pseudomonas aeruginosa elastase and alkaline protease on serum complement and isolated components C1q and C3. Clin Immunol Immunopathol 62: 133–138.
[33]  Schmidtchen A, Holst E, Tapper H, Bjorck L (2003) Elastase-producing Pseudomonas aeruginosa degrade plasma proteins and extracellular products of human skin and fibroblasts, and inhibit fibroblast growth. Microb Pathog 34: 47–55.
[34]  Wolfgang MC, Jyot J, Goodman AL, Ramphal R, Lory S (2004) Pseudomonas aeruginosa regulates flagellin expression as part of a global response to airway fluid from cystic fibrosis patients. Proc Natl Acad Sci U S A 101: 6664–6668.
[35]  Palmer KL, Mashburn LM, Singh PK, Whiteley M (2005) Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology. J Bacteriol 187: 5267–5277.
[36]  Apidianakis Y, Mindrinos MN, Xiao W, Lau GW, Baldini RL, et al. (2005) Profiling early infection responses: Pseudomonas aeruginosa eludes host defenses by suppressing antimicrobial peptide gene expression. Proc Natl Acad Sci U S A 102: 2573–2578.
[37]  Pauli F, Liu Y, Kim YA, Chen PJ, Kim SK (2006) Chromosomal clustering and GATA transcriptional regulation of intestine-expressed genes in C. elegans. Development 133: 287–295.
[38]  Staskawicz BJ, Mudgett MB, Dangl JL, Galan JE (2001) Common and contrasting themes of plant and animal diseases. Science 292: 2285–2289.
[39]  Alper S, McBride SJ, Lackford B, Freedman JH, Schwartz DA (2007) Specificity and complexity of the Caenorhabditis elegans innate immune response. Mol Cell Biol 27: 5544–5553.
[40]  Rahme LG, Stevens EJ, Wolfort SF, Shao J, Tompkins RG, et al. (1995) Common virulence factors for bacterial pathogenicity in plants and animals. Science 268: 1899–1902.
[41]  Rahme LG, Tan MW, Le L, Wong SM, Tompkins RG, et al. (1997) Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci U S A 94: 13245–13250.
[42]  Tan MW, Rahme LG, Sternberg JA, Tompkins RG, Ausubel FM (1999) Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc Natl Acad Sci U S A 96: 2408–2413.
[43]  Grant SR, Fisher EJ, Chang JH, Mole BM, Dangl JL (2006) Subterfuge and manipulation: type III effector proteins of phytopathogenic bacteria. Annu Rev Microbiol 60: 425–449.
[44]  Angot A, Vergunst A, Genin S, Peeters N (2007) Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems. PLoS Pathog 3: e3. doi:10.1371/journal.ppat.0030003.
[45]  Fauvarque MO, Bergeret E, Chabert J, Dacheux D, Satre M, et al. (2002) Role and activation of type III secretion system genes in Pseudomonas aeruginosa-induced Drosophila killing. Microb Pathog 32: 287–295.
[46]  Miyata S, Casey M, Frank DW, Ausubel FM, Drenkard E (2003) Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis. Infect Immun 71: 2404–2413.
[47]  Hauser AR, Cobb E, Bodi M, Mariscal D, Valles J, et al. (2002) Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med 30: 521–528.
[48]  Lee VT, Smith RS, Tummler B, Lory S (2005) Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion system in vitro and during infection. Infect Immun 73: 1695–1705.
[49]  Bleves S, Soscia C, Nogueira-Orlandi P, Lazdunski A, Filloux A (2005) Quorum sensing negatively controls type III secretion regulon expression in Pseudomonas aeruginosa PAO1. J Bacteriol 187: 3898–3902.
[50]  Yahr TL, Wolfgang MC (2006) Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system. Mol Microbiol 62: 631–640.
[51]  Wareham DW, Papakonstantinopoulou A, Curtis MA (2005) The Pseudomonas aeruginosa PA14 type III secretion system is expressed but not essential to virulence in the Caenorhabditis elegans-P. aeruginosa pathogenicity model. FEMS Microbiol Lett 242: 209–216.
[52]  Kay E, Humair B, Denervaud V, Riedel K, Spahr S, et al. (2006) Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas aeruginosa. J Bacteriol 188: 6026–6033.
[53]  McGrath S, Wade DS, Pesci EC (2004) Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS). FEMS Microbiol Lett 230: 27–34.
[54]  Wade DS, Calfee MW, Rocha ER, Ling EA, Engstrom E, et al. (2005) Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa. J Bacteriol 187: 4372–4380.
[55]  D'Argenio DA, Calfee MW, Rainey PB, Pesci EC (2002) Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants. J Bacteriol 184: 6481–6489.
[56]  Lepine F, Dekimpe V, Lesic B, Milot S, Lesimple A, et al. (2007) PqsA is required for the biosynthesis of 2,4-dihydroxyquinoline (DHQ), a newly identified metabolite produced by Pseudomonas aeruginosa and Burkholderia thailandensis. Biol Chem 388: 839–845.
[57]  Coleman JP, Hudson LL, McKnight SL, Farrow JM 3rd, Calfee MW, et al. (2008) Pseudomonas aeruginosa PqsA is an anthranilate-coenzyme A ligase. J Bacteriol 190: 1247–1255.
[58]  Schuster M, Lostroh CP, Ogi T, Greenberg EP (2003) Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J Bacteriol 185: 2066–2079.
[59]  Wagner VE, Bushnell D, Passador L, Brooks AI, Iglewski BH (2003) Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J Bacteriol 185: 2080–2095.
[60]  McElwee JJ, Schuster E, Blanc E, Thomas JH, Gems D (2004) Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279: 44533–44543.
[61]  Pujol N, Zugasti O, Wong D, Couillault C, Kurz CL, et al. (2008) Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides. PLoS Pathog 4: e1000105. doi:10.1371/journal.ppat.1000105.
[62]  Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382: 536–539.
[63]  Wolkow CA, Munoz MJ, Riddle DL, Ruvkun G (2002) Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway. J Biol Chem 277: 49591–49597.
[64]  Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G (1999) A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13: 1438–1452.
[65]  Paradis S, Ruvkun G (1998) Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12: 2488–2498.
[66]  Hertweck M, Gobel C, Baumeister R (2004) C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 6: 577–588.
[67]  Lee RY, Hench J, Ruvkun G (2001) Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr Biol 11: 1950–1957.
[68]  Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28: 139–145.
[69]  McElwee J, Bubb K, Thomas JH (2003) Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2: 111–121.
[70]  Furuyama T, Nakazawa T, Nakano I, Mori N (2000) Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues. Biochem J 349: 629–634.
[71]  Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. Faseb J 13: 1385–1393.
[72]  Leiers B, Kampkotter A, Grevelding CG, Link CD, Johnson TE, et al. (2003) A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free Radic Biol Med 34: 1405–1415.
[73]  Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11: 1975–1980.
[74]  Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399: 362–366.
[75]  Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300: 1142–1145.
[76]  Shapira M, Tan MW (2008) Genetic analysis of Caenorhabditis elegans innate immunity. Methods Mol Biol 415: 429–442.
[77]  Berman JR, Kenyon C (2006) Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124: 1055–1068.
[78]  Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277: 942–946.
[79]  Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, et al. (2001) Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev 15: 672–686.
[80]  Murphy CT, Lee SJ, Kenyon C (2007) Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans. Proc Natl Acad Sci U S A 104: 19046–19050.
[81]  Miyata S, Begun J, Troemel ER, Ausubel FM (2008) DAF-16-Dependent Suppression of Immunity during Reproduction in C. elegans. Genetics.
[82]  Tan MW, Mahajan-Miklos S, Ausubel FM (1999) Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A 96: 715–720.
[83]  Espelt MV, Estevez AY, Yin X, Strange K (2005) Oscillatory Ca2+ signaling in the isolated Caenorhabditis elegans intestine: role of the inositol-1,4,5-trisphosphate receptor and phospholipases C beta and gamma. J Gen Physiol 126: 379–392.
[84]  Qadota H, Inoue M, Hikita T, Koppen M, Hardin JD, et al. (2007) Establishment of a tissue-specific RNAi system in C. elegans. Gene 400: 166–173.
[85]  Lorin-Nebel C, Xing J, Yan X, Strange K (2007) CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility. J Physiol 580: 67–85.
[86]  Waterston RH, Thomson JN, Brenner S (1980) Mutants with altered muscle structure of Caenorhabditis elegans. Dev Biol 77: 271–302.
[87]  Pujol N, Cypowyj S, Ziegler K, Millet A, Astrain A, et al. (2008) Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol 18: 481–489.
[88]  Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402: 804–809.
[89]  Ailion M, Inoue T, Weaver CI, Holdcraft RW, Thomas JH (1999) Neurosecretory control of aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A 96: 7394–7397.
[90]  Bargmann CI, Horvitz HR (1991) Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 251: 1243–1246.
[91]  He P, Shan L, Sheen J (2007) Elicitation and suppression of microbe-associated molecular pattern-triggered immunity in plant-microbe interactions. Cell Microbiol 9: 1385–1396.
[92]  Wolff S, Ma H, Burch D, Maciel GA, Hunter T, et al. (2006) SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124: 1039–1053.
[93]  Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, et al. (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132: 1025–1038.
[94]  Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295: 502–505.
[95]  Greer EL, Brunet A (2008) FOXO transcription factors in ageing and cancer. Acta Physiol (Oxf) 192: 19–28.
[96]  Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.
[97]  Demeter J, Beauheim C, Gollub J, Hernandez-Boussard T, Jin H, et al. (2007) The Stanford Microarray Database: implementation of new analysis tools and open source release of software. Nucleic Acids Res 35: D766–770.
[98]  Wrobel G, Kokocinski F, Lichter P (2004) AutoPrime: selecting primers for expressed sequences. Genome Biology 5: P11.
[99]  Li W, Gao B, Lee SM, Bennett K, Fang D (2007) RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Dev Cell 12: 235–246.

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