DOI: 10.1073/pnas.180130797. Toll-related receptors and the control of antimicrobial peptide expression in<i>Drosophila</i>

10.1073/pnas.180130797

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides.Drosophilahas appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additionalToll-related genes (Toll-3toToll-8) inDrosophilain addition to18-wheeler. Two of these genes,Toll-3andToll-4, are expressed at a low level.Toll-6,-7, and-8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, likeTolland18w, they perform developmental functions. Finally,Toll-5is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.

Bibliography

Tauszig, S., Jouanguy, E., Hoffmann, J. A., & Imler, J.-L. (2000). Toll-related receptors and the control of antimicrobial peptide expression inDrosophila. Proceedings of the National Academy of Sciences, 97(19), 10520â10525.

Authors 4

Servane Tauszig (first)
Emmanuelle Jouanguy (additional)
Jules A. Hoffmann (additional)
Jean-Luc Imler (additional)

References 46 Referenced 321

J Hoffmann, J Reichhart Trends Cell Biol 7, 309–316 (1997). (10.1016/S0962-8924(97)01087-8) / Trends Cell Biol by Hoffmann J (1997)
B Lemaitre, J Reichhart, J Hoffmann Proc Natl Acad Sci USA 94, 14614–14619 (1997). (10.1073/pnas.94.26.14614) / Proc Natl Acad Sci USA by Lemaitre B (1997)
B Lemaitre, E Nicolas, L Michaut, J Reichhart, J Hoffmann Cell 86, 973–983 (1996). (10.1016/S0092-8674(00)80172-5) / Cell by Lemaitre B (1996)
Y DeLotto, R DeLotto Mech Dev 72, 141–148 (1998). (10.1016/S0925-4773(98)00024-0) / Mech Dev by DeLotto Y (1998)
E A Levashina, E Langley, C Green, D Gubb, M Ashburner, J A Hoffmann, J M Reichhart Science 285, 1917–1919 (1999). (10.1126/science.285.5435.1917) / Science by Levashina E A (1999)
J Imler, J Hoffmann Curr Opin Microbiol 3, 16–22 (2000). (10.1016/S1369-5274(99)00045-4) / Curr Opin Microbiol by Imler J (2000)
X Meng, B S Khanuja, Y T Ip Genes Dev 13, 792–797 (1999). (10.1101/gad.13.7.792) / Genes Dev by Meng X (1999)
P Manfruelli, J M Reichhart, R Steward, J A Hoffmann, B Lemaitre EMBO J 18, 3380–3391 (1999). (10.1093/emboj/18.12.3380) / EMBO J by Manfruelli P (1999)
S Rutschmann, A Jung, C Hetru, J Reichhart, J Hoffmann, D Ferrandon Immunity 12, 569–580 (2000). (10.1016/S1074-7613(00)80208-3) / Immunity by Rutschmann S (2000)
R Medzhitov, P Preston-Hurlburt, C Janeway Nature (London) 388, 394–397 (1997). (10.1038/41131) / Nature (London) by Medzhitov R (1997)
F Rock, G Hardiman, J Timans, R Kastelein, J Bazan Proc Natl Acad Sci USA 95, 588–593 (1998). (10.1073/pnas.95.2.588) / Proc Natl Acad Sci USA by Rock F (1998)
P M Chaudhary, C Ferguson, V Nguyen, O Nguyen, H F Massa, M Eby, A Jasmin, B J Trask, L Hood, P S Nelson Blood 91, 4020–4027 (1998). (10.1182/blood.V91.11.4020) / Blood by Chaudhary P M (1998)
O Takeuchi, T Kawai, H Sanjo, N G Copeland, D J Gilbert, N A Jenkins, K Takeda, S Akira Gene 231, 59–65 (1999). (10.1016/S0378-1119(99)00098-0) / Gene by Takeuchi O (1999)
K Hoshino, O Takeuchi, T Kawai, H Sanjo, T Ogawa, Y Takeda, K Takeda, S Akira J Immunol 162, 3749–3752 (1999). (10.4049/jimmunol.162.7.3749) / J Immunol by Hoshino K (1999)
A Poltorak, X He, I Smirnova, M Liu, C Huffel, X Du, D Birdwell, E Alejos, M Silva, C Galanos, et al. Science 282, 2085–2088 (1998). (10.1126/science.282.5396.2085) / Science by Poltorak A (1998)
O Takeuchi, K Hoshino, T Kawai, H Sanjo, H Takada, T Ogawa, K Takeda, S Akira Immunity 11, 443–451 (1999). (10.1016/S1074-7613(00)80119-3) / Immunity by Takeuchi O (1999)
E Eldon, S Kooyer, D D'Evelyn, M Duman, P Lawinger, J Botas, H Bellen Development (Cambridge, UK) 120, 885–899 (1994). (10.1242/dev.120.4.885) / Development (Cambridge, UK) by Eldon E (1994)
S F Altschul, W Gish, W Miller, E W Myers, D J Lipman J Mol Biol 215, 403–410 (1990). (10.1016/S0022-2836(05)80360-2) / J Mol Biol by Altschul S F (1990)
J Mitcham, P Parnet, T Bonnert, K Garka, M Gerhart, J Slack, M Gayle, S Dower, J Sims J Biol Chem 271, 5777–5783 (1996). (10.1074/jbc.271.10.5777) / J Biol Chem by Mitcham J (1996)
C Luo, L Zheng Immunogenetics 51, 92–98 (2000). (10.1007/s002510050017) / Immunogenetics by Luo C (2000)
J Sambrook, E Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989). / Molecular Cloning: A Laboratory Manual by Sambrook J (1989)
J Dimarcq, J Imler, R Lanot, R Ezekowitz, J Hoffmann, C Janeway, M Lagueux Insect Biochem Mol Biol 27, 877–886 (1997). (10.1016/S0965-1748(97)00072-6) / Insect Biochem Mol Biol by Dimarcq J (1997)
J Reichhart, M Meister, J Dimarcq, D Zachary, D Hoffmann, C Ruiz, G Richards, J Hoffmann EMBO J 11, 1469–1477 (1992). (10.1002/j.1460-2075.1992.tb05191.x) / EMBO J by Reichhart J (1992)
D Ferrandon, A Jung, M Criqui, B Lemaitre, S Uttenweiler-Joseph, L Michaut, J Reichhart, J Hoffmann EMBO J 17, 1217–1227 (1998). (10.1093/emboj/17.5.1217) / EMBO J by Ferrandon D (1998)
M Charlet, M Lagueux, J Reichhart, D Hoffmann, A Braun, M Meister Eur J Biochem 241, 699–706 (1996). (10.1111/j.1432-1033.1996.00699.x) / Eur J Biochem by Charlet M (1996)
J Dimarcq, D Hoffmann, M Meister, P Bulet, R Lanot, J Reichhart, J Hoffmann Eur J Biochem 221, 201–209 (1994). (10.1111/j.1432-1033.1994.tb18730.x) / Eur J Biochem by Dimarcq J (1994)
Y Engstrom, L Kadayalil, S Sun, C Samakovlis, D Hultmark, I Faye J Mol Biol 232, 327–333 (1993). (10.1006/jmbi.1993.1392) / J Mol Biol by Engstrom Y (1993)
M A Krasnow, E E Saffman, K Kornfeld, D S Hogness Cell 57, 1031–1043 (1989). (10.1016/0092-8674(89)90341-3) / Cell by Krasnow M A (1989)
K A Winans, C Hashimoto Mol Biol Cell 6, 587–596 (1995). (10.1091/mbc.6.5.587) / Mol Biol Cell by Winans K A (1995)
D Morisato, K Anderson Cell 76, 677–688 (1994). (10.1016/0092-8674(94)90507-X) / Cell by Morisato D (1994)
C Thisse, F Perrin-Schmitt, C Stoetzel, B Thisse Cell 65, 1191–1201 (1991). (10.1016/0092-8674(91)90014-P) / Cell by Thisse C (1991)
S G Buchanan, N J Gay Prog Biophys Mol Biol 65, 1–44 (1996). (10.1016/S0079-6107(96)00003-X) / Prog Biophys Mol Biol by Buchanan S G (1996)
M Williams, A Rodriguez, D Kimbrell, E Eldon EMBO J 16, 6120–6130 (1997). (10.1093/emboj/16.20.6120) / EMBO J by Williams M (1997)
C Chiang, P A Beachy Mech Dev 47, 225–239 (1994). (10.1016/0925-4773(94)90041-8) / Mech Dev by Chiang C (1994)
B C Meyers, A W Dickerman, R W Michelmore, S Sivaramakrishnan, B W Sobral, N D Young Plant J 20, 317–332 (1999). (10.1046/j.1365-313X.1999.t01-1-00606.x) / Plant J by Meyers B C (1999)
M Tan, F Ausubel Curr Opin Immunol 3, 29–34 (2000). / Curr Opin Immunol by Tan M (2000)
D M Underhill, A Ozinsky, A M Hajjar, A Stevens, C B Wilson, M Bassetti, A Aderem Nature (London) 401, 811–815 (1999). (10.1038/44605) / Nature (London) by Underhill D M (1999)
M P Belvin, K V Anderson Annu Rev Cell Dev Biol 12, 393–416 (1996). (10.1146/annurev.cellbio.12.1.393) / Annu Rev Cell Dev Biol by Belvin M P (1996)
S Gerttula, Y S Jin, K V Anderson Genetics 119, 123–133 (1988). (10.1093/genetics/119.1.123) / Genetics by Gerttula S (1988)
J Keith, N Gay EMBO J 9, 4299–4306 (1990). (10.1002/j.1460-2075.1990.tb07878.x) / EMBO J by Keith J (1990)
M Hedengren, B Asling, M Dushay, I Ando, S Ekengren, M Wihlborg, D Hultmark Mol Cell 4, 1–20 (1999). (10.1016/S1097-2765(00)80392-5) / Mol Cell by Hedengren M (1999)
R Medzhitov, P Preston-Hurlburt, E Kopp, A Stadlen, C Chen, S Ghosh, C A Janeway Mol Cell 2, 253–258 (1998). (10.1016/S1097-2765(00)80136-7) / Mol Cell by Medzhitov R (1998)
R B Yang, M R Mark, A L Gurney, P J Godowski J Immunol 163, 639–643 (1999). (10.4049/jimmunol.163.2.639) / J Immunol by Yang R B (1999)
F X Zhang, C J Kirschning, R Mancinelli, X P Xu, Y Jin, E Faure, A Mantovani, M Rothe, M Muzio, M Arditi J Biol Chem 274, 7611–7614 (1999). (10.1074/jbc.274.12.7611) / J Biol Chem by Zhang F X (1999)
L P Wu, K V Anderson Nature (London) 392, 93–97 (1998). (10.1038/32195) / Nature (London) by Wu L P (1998)
D Schneider, K Hudson, T Lin, K Anderson Genes Dev 5, 797–807 (1991). (10.1101/gad.5.5.797) / Genes Dev by Schneider D (1991)

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:43 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:34 a.m.)
Indexed	19 minutes ago (Aug. 25, 2025, 6:18 p.m.)
Issued	24 years, 11 months ago (Sept. 5, 2000)
Published	24 years, 11 months ago (Sept. 5, 2000)
Published Online	24 years, 11 months ago (Sept. 5, 2000)
Published Print	24 years, 11 months ago (Sept. 12, 2000)

Funders 0

None

BibTeX

@article{Tauszig_2000, title={Toll-related receptors and the control of antimicrobial peptide expression inDrosophila}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.180130797}, DOI={10.1073/pnas.180130797}, number={19}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Tauszig, Servane and Jouanguy, Emmanuelle and Hoffmann, Jules A. and Imler, Jean-Luc}, year={2000}, month=sep, pages={10520–10525} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        25
      ]
    ],
    "date-time": "2025-08-25T22:18:09Z",
    "timestamp": 1756160289206
  },
  "reference-count": 46,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "19",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        9,
        12
      ]
    ]
  },
  "abstract": "<jats:p>Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides.<jats:italic>Drosophila</jats:italic>has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional<jats:italic>Toll-</jats:italic>related genes (<jats:italic>Toll-3</jats:italic>to<jats:italic>Toll-8</jats:italic>) in<jats:italic>Drosophila</jats:italic>in addition to<jats:italic>18-wheeler</jats:italic>. Two of these genes,<jats:italic>Toll-3</jats:italic>and<jats:italic>Toll-4</jats:italic>, are expressed at a low level.<jats:italic>Toll-6</jats:italic>,<jats:italic>-7</jats:italic>, and<jats:italic>-8</jats:italic>, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like<jats:italic>Toll</jats:italic>and<jats:italic>18w</jats:italic>, they perform developmental functions. Finally,<jats:italic>Toll-5</jats:italic>is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.</jats:p>",
  "DOI": "10.1073/pnas.180130797",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:43:20Z",
    "timestamp": 1027694600000
  },
  "page": "10520-10525",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 321,
  "title": "Toll-related receptors and the control of antimicrobial peptide expression in<i>Drosophila</i>",
  "prefix": "10.1073",
  "volume": "97",
  "author": [
    {
      "given": "Servane",
      "family": "Tauszig",
      "sequence": "first",
      "affiliation": [
        {
          "name": "UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Mol\u00e9culaire et Cellulaire, F-67084 Strasbourg, France"
        }
      ]
    },
    {
      "given": "Emmanuelle",
      "family": "Jouanguy",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Mol\u00e9culaire et Cellulaire, F-67084 Strasbourg, France"
        }
      ]
    },
    {
      "given": "Jules A.",
      "family": "Hoffmann",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Mol\u00e9culaire et Cellulaire, F-67084 Strasbourg, France"
        }
      ]
    },
    {
      "given": "Jean-Luc",
      "family": "Imler",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Mol\u00e9culaire et Cellulaire, F-67084 Strasbourg, France"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2000,
        9,
        5
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_5_1_2",
      "doi-asserted-by": "crossref",
      "first-page": "309",
      "DOI": "10.1016/S0962-8924(97)01087-8",
      "volume": "7",
      "author": "Hoffmann J",
      "year": "1997",
      "unstructured": "J Hoffmann, J Reichhart Trends Cell Biol 7, 309\u2013316 (1997).",
      "journal-title": "Trends Cell Biol"
    },
    {
      "key": "e_1_3_5_2_2",
      "doi-asserted-by": "crossref",
      "first-page": "14614",
      "DOI": "10.1073/pnas.94.26.14614",
      "volume": "94",
      "author": "Lemaitre B",
      "year": "1997",
      "unstructured": "B Lemaitre, J Reichhart, J Hoffmann Proc Natl Acad Sci USA 94, 14614\u201314619 (1997).",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "e_1_3_5_3_2",
      "doi-asserted-by": "crossref",
      "first-page": "973",
      "DOI": "10.1016/S0092-8674(00)80172-5",
      "volume": "86",
      "author": "Lemaitre B",
      "year": "1996",
      "unstructured": "B Lemaitre, E Nicolas, L Michaut, J Reichhart, J Hoffmann Cell 86, 973\u2013983 (1996).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_5_4_2",
      "doi-asserted-by": "crossref",
      "first-page": "141",
      "DOI": "10.1016/S0925-4773(98)00024-0",
      "volume": "72",
      "author": "DeLotto Y",
      "year": "1998",
      "unstructured": "Y DeLotto, R DeLotto Mech Dev 72, 141\u2013148 (1998).",
      "journal-title": "Mech Dev"
    },
    {
      "key": "e_1_3_5_5_2",
      "doi-asserted-by": "crossref",
      "first-page": "1917",
      "DOI": "10.1126/science.285.5435.1917",
      "volume": "285",
      "author": "Levashina E A",
      "year": "1999",
      "unstructured": "E A Levashina, E Langley, C Green, D Gubb, M Ashburner, J A Hoffmann, J M Reichhart Science 285, 1917\u20131919 (1999).",
      "journal-title": "Science"
    },
    {
      "key": "e_1_3_5_6_2",
      "doi-asserted-by": "crossref",
      "first-page": "16",
      "DOI": "10.1016/S1369-5274(99)00045-4",
      "volume": "3",
      "author": "Imler J",
      "year": "2000",
      "unstructured": "J Imler, J Hoffmann Curr Opin Microbiol 3, 16\u201322 (2000).",
      "journal-title": "Curr Opin Microbiol"
    },
    {
      "key": "e_1_3_5_7_2",
      "doi-asserted-by": "crossref",
      "first-page": "792",
      "DOI": "10.1101/gad.13.7.792",
      "volume": "13",
      "author": "Meng X",
      "year": "1999",
      "unstructured": "X Meng, B S Khanuja, Y T Ip Genes Dev 13, 792\u2013797 (1999).",
      "journal-title": "Genes Dev"
    },
    {
      "key": "e_1_3_5_8_2",
      "doi-asserted-by": "crossref",
      "first-page": "3380",
      "DOI": "10.1093/emboj/18.12.3380",
      "volume": "18",
      "author": "Manfruelli P",
      "year": "1999",
      "unstructured": "P Manfruelli, J M Reichhart, R Steward, J A Hoffmann, B Lemaitre EMBO J 18, 3380\u20133391 (1999).",
      "journal-title": "EMBO J"
    },
    {
      "key": "e_1_3_5_9_2",
      "doi-asserted-by": "crossref",
      "first-page": "569",
      "DOI": "10.1016/S1074-7613(00)80208-3",
      "volume": "12",
      "author": "Rutschmann S",
      "year": "2000",
      "unstructured": "S Rutschmann, A Jung, C Hetru, J Reichhart, J Hoffmann, D Ferrandon Immunity 12, 569\u2013580 (2000).",
      "journal-title": "Immunity"
    },
    {
      "key": "e_1_3_5_10_2",
      "doi-asserted-by": "crossref",
      "first-page": "394",
      "DOI": "10.1038/41131",
      "volume": "388",
      "author": "Medzhitov R",
      "year": "1997",
      "unstructured": "R Medzhitov, P Preston-Hurlburt, C Janeway Nature (London) 388, 394\u2013397 (1997).",
      "journal-title": "Nature (London)"
    },
    {
      "key": "e_1_3_5_11_2",
      "doi-asserted-by": "crossref",
      "first-page": "588",
      "DOI": "10.1073/pnas.95.2.588",
      "volume": "95",
      "author": "Rock F",
      "year": "1998",
      "unstructured": "F Rock, G Hardiman, J Timans, R Kastelein, J Bazan Proc Natl Acad Sci USA 95, 588\u2013593 (1998).",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "e_1_3_5_12_2",
      "doi-asserted-by": "crossref",
      "first-page": "4020",
      "DOI": "10.1182/blood.V91.11.4020",
      "volume": "91",
      "author": "Chaudhary P M",
      "year": "1998",
      "unstructured": "P M Chaudhary, C Ferguson, V Nguyen, O Nguyen, H F Massa, M Eby, A Jasmin, B J Trask, L Hood, P S Nelson Blood 91, 4020\u20134027 (1998).",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_3_5_13_2",
      "doi-asserted-by": "crossref",
      "first-page": "59",
      "DOI": "10.1016/S0378-1119(99)00098-0",
      "volume": "231",
      "author": "Takeuchi O",
      "year": "1999",
      "unstructured": "O Takeuchi, T Kawai, H Sanjo, N G Copeland, D J Gilbert, N A Jenkins, K Takeda, S Akira Gene 231, 59\u201365 (1999).",
      "journal-title": "Gene"
    },
    {
      "key": "e_1_3_5_14_2",
      "doi-asserted-by": "crossref",
      "first-page": "3749",
      "DOI": "10.4049/jimmunol.162.7.3749",
      "volume": "162",
      "author": "Hoshino K",
      "year": "1999",
      "unstructured": "K Hoshino, O Takeuchi, T Kawai, H Sanjo, T Ogawa, Y Takeda, K Takeda, S Akira J Immunol 162, 3749\u20133752 (1999).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_5_15_2",
      "doi-asserted-by": "crossref",
      "first-page": "2085",
      "DOI": "10.1126/science.282.5396.2085",
      "volume": "282",
      "author": "Poltorak A",
      "year": "1998",
      "unstructured": "A Poltorak, X He, I Smirnova, M Liu, C Huffel, X Du, D Birdwell, E Alejos, M Silva, C Galanos, et al. Science 282, 2085\u20132088 (1998).",
      "journal-title": "Science"
    },
    {
      "key": "e_1_3_5_16_2",
      "doi-asserted-by": "crossref",
      "first-page": "443",
      "DOI": "10.1016/S1074-7613(00)80119-3",
      "volume": "11",
      "author": "Takeuchi O",
      "year": "1999",
      "unstructured": "O Takeuchi, K Hoshino, T Kawai, H Sanjo, H Takada, T Ogawa, K Takeda, S Akira Immunity 11, 443\u2013451 (1999).",
      "journal-title": "Immunity"
    },
    {
      "key": "e_1_3_5_17_2",
      "doi-asserted-by": "crossref",
      "first-page": "885",
      "DOI": "10.1242/dev.120.4.885",
      "volume": "120",
      "author": "Eldon E",
      "year": "1994",
      "unstructured": "E Eldon, S Kooyer, D D'Evelyn, M Duman, P Lawinger, J Botas, H Bellen Development (Cambridge, UK) 120, 885\u2013899 (1994).",
      "journal-title": "Development (Cambridge, UK)"
    },
    {
      "key": "e_1_3_5_18_2",
      "doi-asserted-by": "crossref",
      "first-page": "403",
      "DOI": "10.1016/S0022-2836(05)80360-2",
      "volume": "215",
      "author": "Altschul S F",
      "year": "1990",
      "unstructured": "S F Altschul, W Gish, W Miller, E W Myers, D J Lipman J Mol Biol 215, 403\u2013410 (1990).",
      "journal-title": "J Mol Biol"
    },
    {
      "key": "e_1_3_5_19_2",
      "doi-asserted-by": "crossref",
      "first-page": "5777",
      "DOI": "10.1074/jbc.271.10.5777",
      "volume": "271",
      "author": "Mitcham J",
      "year": "1996",
      "unstructured": "J Mitcham, P Parnet, T Bonnert, K Garka, M Gerhart, J Slack, M Gayle, S Dower, J Sims J Biol Chem 271, 5777\u20135783 (1996).",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "e_1_3_5_20_2",
      "doi-asserted-by": "crossref",
      "first-page": "92",
      "DOI": "10.1007/s002510050017",
      "volume": "51",
      "author": "Luo C",
      "year": "2000",
      "unstructured": "C Luo, L Zheng Immunogenetics 51, 92\u201398 (2000).",
      "journal-title": "Immunogenetics"
    },
    {
      "key": "e_1_3_5_21_2",
      "volume-title": "Molecular Cloning: A Laboratory Manual",
      "author": "Sambrook J",
      "year": "1989",
      "unstructured": "J Sambrook, E Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989).",
      "edition": "2"
    },
    {
      "key": "e_1_3_5_22_2",
      "doi-asserted-by": "crossref",
      "first-page": "877",
      "DOI": "10.1016/S0965-1748(97)00072-6",
      "volume": "27",
      "author": "Dimarcq J",
      "year": "1997",
      "unstructured": "J Dimarcq, J Imler, R Lanot, R Ezekowitz, J Hoffmann, C Janeway, M Lagueux Insect Biochem Mol Biol 27, 877\u2013886 (1997).",
      "journal-title": "Insect Biochem Mol Biol"
    },
    {
      "key": "e_1_3_5_23_2",
      "doi-asserted-by": "crossref",
      "first-page": "1469",
      "DOI": "10.1002/j.1460-2075.1992.tb05191.x",
      "volume": "11",
      "author": "Reichhart J",
      "year": "1992",
      "unstructured": "J Reichhart, M Meister, J Dimarcq, D Zachary, D Hoffmann, C Ruiz, G Richards, J Hoffmann EMBO J 11, 1469\u20131477 (1992).",
      "journal-title": "EMBO J"
    },
    {
      "key": "e_1_3_5_24_2",
      "doi-asserted-by": "crossref",
      "first-page": "1217",
      "DOI": "10.1093/emboj/17.5.1217",
      "volume": "17",
      "author": "Ferrandon D",
      "year": "1998",
      "unstructured": "D Ferrandon, A Jung, M Criqui, B Lemaitre, S Uttenweiler-Joseph, L Michaut, J Reichhart, J Hoffmann EMBO J 17, 1217\u20131227 (1998).",
      "journal-title": "EMBO J"
    },
    {
      "key": "e_1_3_5_25_2",
      "doi-asserted-by": "crossref",
      "first-page": "699",
      "DOI": "10.1111/j.1432-1033.1996.00699.x",
      "volume": "241",
      "author": "Charlet M",
      "year": "1996",
      "unstructured": "M Charlet, M Lagueux, J Reichhart, D Hoffmann, A Braun, M Meister Eur J Biochem 241, 699\u2013706 (1996).",
      "journal-title": "Eur J Biochem"
    },
    {
      "key": "e_1_3_5_26_2",
      "doi-asserted-by": "crossref",
      "first-page": "201",
      "DOI": "10.1111/j.1432-1033.1994.tb18730.x",
      "volume": "221",
      "author": "Dimarcq J",
      "year": "1994",
      "unstructured": "J Dimarcq, D Hoffmann, M Meister, P Bulet, R Lanot, J Reichhart, J Hoffmann Eur J Biochem 221, 201\u2013209 (1994).",
      "journal-title": "Eur J Biochem"
    },
    {
      "key": "e_1_3_5_27_2",
      "doi-asserted-by": "crossref",
      "first-page": "327",
      "DOI": "10.1006/jmbi.1993.1392",
      "volume": "232",
      "author": "Engstrom Y",
      "year": "1993",
      "unstructured": "Y Engstrom, L Kadayalil, S Sun, C Samakovlis, D Hultmark, I Faye J Mol Biol 232, 327\u2013333 (1993).",
      "journal-title": "J Mol Biol"
    },
    {
      "key": "e_1_3_5_28_2",
      "doi-asserted-by": "crossref",
      "first-page": "1031",
      "DOI": "10.1016/0092-8674(89)90341-3",
      "volume": "57",
      "author": "Krasnow M A",
      "year": "1989",
      "unstructured": "M A Krasnow, E E Saffman, K Kornfeld, D S Hogness Cell 57, 1031\u20131043 (1989).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_5_29_2",
      "doi-asserted-by": "crossref",
      "first-page": "587",
      "DOI": "10.1091/mbc.6.5.587",
      "volume": "6",
      "author": "Winans K A",
      "year": "1995",
      "unstructured": "K A Winans, C Hashimoto Mol Biol Cell 6, 587\u2013596 (1995).",
      "journal-title": "Mol Biol Cell"
    },
    {
      "key": "e_1_3_5_30_2",
      "doi-asserted-by": "crossref",
      "first-page": "677",
      "DOI": "10.1016/0092-8674(94)90507-X",
      "volume": "76",
      "author": "Morisato D",
      "year": "1994",
      "unstructured": "D Morisato, K Anderson Cell 76, 677\u2013688 (1994).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_5_31_2",
      "doi-asserted-by": "crossref",
      "first-page": "1191",
      "DOI": "10.1016/0092-8674(91)90014-P",
      "volume": "65",
      "author": "Thisse C",
      "year": "1991",
      "unstructured": "C Thisse, F Perrin-Schmitt, C Stoetzel, B Thisse Cell 65, 1191\u20131201 (1991).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_5_32_2",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1016/S0079-6107(96)00003-X",
      "volume": "65",
      "author": "Buchanan S G",
      "year": "1996",
      "unstructured": "S G Buchanan, N J Gay Prog Biophys Mol Biol 65, 1\u201344 (1996).",
      "journal-title": "Prog Biophys Mol Biol"
    },
    {
      "key": "e_1_3_5_33_2",
      "doi-asserted-by": "crossref",
      "first-page": "6120",
      "DOI": "10.1093/emboj/16.20.6120",
      "volume": "16",
      "author": "Williams M",
      "year": "1997",
      "unstructured": "M Williams, A Rodriguez, D Kimbrell, E Eldon EMBO J 16, 6120\u20136130 (1997).",
      "journal-title": "EMBO J"
    },
    {
      "key": "e_1_3_5_34_2",
      "doi-asserted-by": "crossref",
      "first-page": "225",
      "DOI": "10.1016/0925-4773(94)90041-8",
      "volume": "47",
      "author": "Chiang C",
      "year": "1994",
      "unstructured": "C Chiang, P A Beachy Mech Dev 47, 225\u2013239 (1994).",
      "journal-title": "Mech Dev"
    },
    {
      "key": "e_1_3_5_35_2",
      "doi-asserted-by": "crossref",
      "first-page": "317",
      "DOI": "10.1046/j.1365-313X.1999.t01-1-00606.x",
      "volume": "20",
      "author": "Meyers B C",
      "year": "1999",
      "unstructured": "B C Meyers, A W Dickerman, R W Michelmore, S Sivaramakrishnan, B W Sobral, N D Young Plant J 20, 317\u2013332 (1999).",
      "journal-title": "Plant J"
    },
    {
      "key": "e_1_3_5_36_2",
      "first-page": "29",
      "volume": "3",
      "author": "Tan M",
      "year": "2000",
      "unstructured": "M Tan, F Ausubel Curr Opin Immunol 3, 29\u201334 (2000).",
      "journal-title": "Curr Opin Immunol"
    },
    {
      "key": "e_1_3_5_37_2",
      "doi-asserted-by": "crossref",
      "first-page": "811",
      "DOI": "10.1038/44605",
      "volume": "401",
      "author": "Underhill D M",
      "year": "1999",
      "unstructured": "D M Underhill, A Ozinsky, A M Hajjar, A Stevens, C B Wilson, M Bassetti, A Aderem Nature (London) 401, 811\u2013815 (1999).",
      "journal-title": "Nature (London)"
    },
    {
      "key": "e_1_3_5_38_2",
      "doi-asserted-by": "crossref",
      "first-page": "393",
      "DOI": "10.1146/annurev.cellbio.12.1.393",
      "volume": "12",
      "author": "Belvin M P",
      "year": "1996",
      "unstructured": "M P Belvin, K V Anderson Annu Rev Cell Dev Biol 12, 393\u2013416 (1996).",
      "journal-title": "Annu Rev Cell Dev Biol"
    },
    {
      "key": "e_1_3_5_39_2",
      "doi-asserted-by": "crossref",
      "first-page": "123",
      "DOI": "10.1093/genetics/119.1.123",
      "volume": "119",
      "author": "Gerttula S",
      "year": "1988",
      "unstructured": "S Gerttula, Y S Jin, K V Anderson Genetics 119, 123\u2013133 (1988).",
      "journal-title": "Genetics"
    },
    {
      "key": "e_1_3_5_40_2",
      "doi-asserted-by": "crossref",
      "first-page": "4299",
      "DOI": "10.1002/j.1460-2075.1990.tb07878.x",
      "volume": "9",
      "author": "Keith J",
      "year": "1990",
      "unstructured": "J Keith, N Gay EMBO J 9, 4299\u20134306 (1990).",
      "journal-title": "EMBO J"
    },
    {
      "key": "e_1_3_5_41_2",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1016/S1097-2765(00)80392-5",
      "volume": "4",
      "author": "Hedengren M",
      "year": "1999",
      "unstructured": "M Hedengren, B Asling, M Dushay, I Ando, S Ekengren, M Wihlborg, D Hultmark Mol Cell 4, 1\u201320 (1999).",
      "journal-title": "Mol Cell"
    },
    {
      "key": "e_1_3_5_42_2",
      "doi-asserted-by": "crossref",
      "first-page": "253",
      "DOI": "10.1016/S1097-2765(00)80136-7",
      "volume": "2",
      "author": "Medzhitov R",
      "year": "1998",
      "unstructured": "R Medzhitov, P Preston-Hurlburt, E Kopp, A Stadlen, C Chen, S Ghosh, C A Janeway Mol Cell 2, 253\u2013258 (1998).",
      "journal-title": "Mol Cell"
    },
    {
      "key": "e_1_3_5_43_2",
      "doi-asserted-by": "crossref",
      "first-page": "639",
      "DOI": "10.4049/jimmunol.163.2.639",
      "volume": "163",
      "author": "Yang R B",
      "year": "1999",
      "unstructured": "R B Yang, M R Mark, A L Gurney, P J Godowski J Immunol 163, 639\u2013643 (1999).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_5_44_2",
      "doi-asserted-by": "crossref",
      "first-page": "7611",
      "DOI": "10.1074/jbc.274.12.7611",
      "volume": "274",
      "author": "Zhang F X",
      "year": "1999",
      "unstructured": "F X Zhang, C J Kirschning, R Mancinelli, X P Xu, Y Jin, E Faure, A Mantovani, M Rothe, M Muzio, M Arditi J Biol Chem 274, 7611\u20137614 (1999).",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "e_1_3_5_45_2",
      "doi-asserted-by": "crossref",
      "first-page": "93",
      "DOI": "10.1038/32195",
      "volume": "392",
      "author": "Wu L P",
      "year": "1998",
      "unstructured": "L P Wu, K V Anderson Nature (London) 392, 93\u201397 (1998).",
      "journal-title": "Nature (London)"
    },
    {
      "key": "e_1_3_5_46_2",
      "doi-asserted-by": "crossref",
      "first-page": "797",
      "DOI": "10.1101/gad.5.5.797",
      "volume": "5",
      "author": "Schneider D",
      "year": "1991",
      "unstructured": "D Schneider, K Hudson, T Lin, K Anderson Genes Dev 5, 797\u2013807 (1991).",
      "journal-title": "Genes Dev"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.180130797",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        4,
        22
      ]
    ],
    "date-time": "2023-04-22T12:34:38Z",
    "timestamp": 1682166878000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.180130797"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        9,
        5
      ]
    ]
  },
  "references-count": 46,
  "journal-issue": {
    "issue": "19",
    "published-print": {
      "date-parts": [
        [
          2000,
          9,
          12
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.180130797"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.180130797",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2000,
        9,
        5
      ]
    ]
  },
  "assertion": [
    {
      "value": "2000-03-23",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2000-09-05",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}