{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:34:36Z","timestamp":1791203676708,"version":"4.2.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,2,14]]},"abstract":"<jats:p>\n                    Although activation of Toll-like receptor 4 (TLR4)-positive cells is essential for eliminating Gram-negative bacteria, overactivation of these cells by the TLR4 ligand LPS initiates a systemic inflammatory reaction and shock. Here we demonstrate that SPRET\/Ei mice, derived from\n                    <jats:italic>Mus spretus<\/jats:italic>\n                    , exhibit a dominant resistance against LPS-induced lethality. This resistance is mediated by bone marrow-derived cells. Macrophages from these mice exhibit normal signaling and gene expression responses that depend on the myeloid differentiation factor 88 adaptor protein, but they are impaired in IFN-\u03b2 production. The defect appears to be specific for IFN-\u03b2, although the SPRET\/Ei IFN-\u03b2 promoter is normal.\n                    <jats:italic>In vivo<\/jats:italic>\n                    IFN-\u03b2 induction by LPS or influenza virus is very low in SPRET\/Ei mice, but IFN-\u03b2-treatment restores the sensitivity to LPS, and IFN type 1 receptor-deficient mice are also resistant to LPS. Because of the defective induction of IFN-\u03b2, these mice are completely resistant to\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    and highly sensitive to\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    infection. Stimulation of SPRET\/Ei macrophages leads to rapid down-regulation of IFN type 1 receptor mRNA expression, which is reflected in poor induction of IFN-\u03b2-dependent genes. This finding indicates that the resistance of SPRET\/Ei mice to LPS is due to disruption of a positive-feedback loop that amplifies IFN-\u03b2 production. In contrast to TLR4-deficient mice, SPRET\/Ei mice resist both LPS and sepsis induced with\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0510874103","type":"journal-article","created":{"date-parts":[[2006,2,2]],"date-time":"2006-02-02T20:48:38Z","timestamp":1138913318000},"page":"2292-2297","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["The wild-derived inbred mouse strain SPRET\/Ei is resistant to LPS and defective in IFN-\u03b2 production"],"prefix":"10.1073","volume":"103","author":[{"given":"Tina","family":"Mahieu","sequence":"first","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Mo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Revets","sequence":"additional","affiliation":[{"name":"Department for Molecular and Cellular Interactions, Flanders Interuniversity Institute for Biotechnology and Free University Brussels, B-1640 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Pasche","sequence":"additional","affiliation":[{"name":"Young Investigator Group Infection Genetics, German Research Centre for Biotechnology, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Lengeling","sequence":"additional","affiliation":[{"name":"Young Investigator Group Infection Genetics, German Research Centre for Biotechnology, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Staelens","sequence":"additional","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Wullaert","sequence":"additional","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke","family":"Vanlaere","sequence":"additional","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tino","family":"Hochepied","sequence":"additional","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"van Roy","sequence":"additional","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Libert","sequence":"additional","affiliation":[{"name":"*Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,2,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.002253"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2003.10.003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2085"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.60.1.8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0290853"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni986"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35092578"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(02)02145-X"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01182"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.1015"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5252.1128"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031023"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5887"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80086-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01889"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni921"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081315"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.8.4304"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999099314360"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.03330.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007790200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90154-6"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.227"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(01)00305-3"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01514-2"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2004.11.008"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni910"},{"key":"e_1_3_3_31_2","first-page":"269","volume":"8","author":"Brouckaert P. G.","year":"1989","unstructured":"P. G. Brouckaert, C. Libert, B. Everaerdt, N. Takahashi, W. Fiers Lymphokine Res 8, 269\u2013274 (1989).","journal-title":"Lymphokine Res"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(00)00149-2"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6522"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.12.7574"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141126"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01049-0"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8009221"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040712"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg038"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.24.9679"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0510874103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:07:11Z","timestamp":1649772431000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0510874103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2,2]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2006,2,14]]}},"alternative-id":["10.1073\/pnas.0510874103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0510874103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,2,2]]},"assertion":[{"value":"2006-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}