{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:25:21Z","timestamp":1792185921810,"version":"4.4.0"},"reference-count":45,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T00:00:00Z","timestamp":1290038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p>\n                    Lipopolysaccharide is a major constituent of the outer membrane of Gram-negative bacteria and important in the induction of pro-inflammatory responses. Recently, novel LPS species derived from\n                    <jats:italic toggle=\"yes\">Neisseria meningitidis<\/jats:italic>\n                    H44\/76 by insertional inactivation of the\n                    <jats:italic toggle=\"yes\">lpxL1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">lpxL2<\/jats:italic>\n                    genes have been created with a lipid A portion consisting of five (penta-acylated\n                    <jats:italic toggle=\"yes\">lpxL1<\/jats:italic>\n                    ) or four (tetra-acylated\n                    <jats:italic toggle=\"yes\">lpxL2<\/jats:italic>\n                    ) fatty acids connected to the glucosamine backbone instead of six fatty acids in the wild-type LPS. We show that these mutant LPS-types are poor inducers of cytokines (tumor-necrosis factor-\u03b1, IL-1\u03b2, IL-10, IL-RA) in human mononuclear cells. Both penta- and tetra-acylated meningococcal LPSs were able to inhibit cytokine production by wild-type\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    or meningococcal LPS. Binding of FITC-labelled\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    LPS TLR4 transfected Chinese hamster ovary (CHO) cells was inhibited by both mutant LPS-types. Experiments with CHO fibroblasts transfected with human CD14 and TLR4 showed that the antagonizing effect was dependent on the expression of human TLR4. In contrast to the situation in humans,\n                    <jats:italic toggle=\"yes\">lpxL1<\/jats:italic>\n                    LPS has agonistic activity for cytokine production in peritoneal macrophages of DBA mice, and exacerbated arthritis in murine collagen induced arthritis model.\n                    <jats:italic toggle=\"yes\">N. meningitidis<\/jats:italic>\n                    lipid A mutant LPSs\n                    <jats:italic toggle=\"yes\">lpxL1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">lpxL2<\/jats:italic>\n                    function as LPS antagonists in humans by inhibiting TLR4-dependent cytokine production but have agonistic activity in mice.\n                  <\/jats:p>","DOI":"10.1177\/1753425910383999","type":"journal-article","created":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T23:14:08Z","timestamp":1290122048000},"page":"517-525","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>Neisseria meningitidis<\/i>\n                    lipid A mutant LPSs function as LPS antagonists in humans by inhibiting TLR 4-dependent cytokine production"],"prefix":"10.1177","volume":"17","author":[{"given":"Tom","family":"Sprong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter van der","family":"Ley","sequence":"additional","affiliation":[{"name":"National Institute for Vaccine Development, Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahla","family":"Abdollahi-Roodsaz","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Joosten","sequence":"additional","affiliation":[{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos van der","family":"Meer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel van","family":"Deuren","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,11,18]]},"reference":[{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.1.144"},{"key":"e_1_2_2_3_2","first-page":"401","article-title":"Neisseria meningitidis lipopolysaccharides in human pathology","volume":"7","author":"Brandtzaeg P","year":"2001","unstructured":"Brandtzaeg P, Bjerre A, Ovstebo R, Brusletto B, Joo GB, Kierulf P. Neisseria meningitidis lipopolysaccharides in human pathology. J Endotoxin Res 2001; 7: 401\u2013420.","journal-title":"J Endotoxin Res"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(11)80355-4"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.371-380.2004"},{"key":"e_1_2_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1698311"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8541"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.11.1777"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2085"},{"key":"e_1_2_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni809"},{"key":"e_1_2_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crvi.2004.04.002"},{"key":"e_1_2_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)55023-7"},{"key":"e_1_2_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.1.218-225.2002"},{"key":"e_1_2_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4490"},{"key":"e_1_2_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7701344"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.6.3001"},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609400200"},{"key":"e_1_2_2_18_2","first-page":"411","article-title":"Neisseria meningitidis can induce pro-inflammatory cytokine production via pathways independent from CD14 and Toll-like receptor 4","volume":"13","author":"Sprong T","year":"2002","unstructured":"Sprong T, van der Ley P, Steeghs L, . Neisseria meningitidis can induce pro-inflammatory cytokine production via pathways independent from CD14 and Toll-like receptor 4. Eur Cytokine Netw 2002; 13: 411\u2013417.","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2230-2236.2001"},{"key":"e_1_2_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2004.00471.x"},{"key":"e_1_2_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.7125"},{"key":"e_1_2_2_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1938"},{"key":"e_1_2_2_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.618"},{"key":"e_1_2_2_24_2","doi-asserted-by":"publisher","DOI":"10.2741\/2353"},{"key":"e_1_2_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.5981-5990.2001"},{"key":"e_1_2_2_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4669"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.9.2.186-188.1979"},{"key":"e_1_2_2_28_2","first-page":"67","article-title":"Production, characterization, and control of MenB-vaccine \u2018Folkehelsa\u2019: an outer membrane vesicle vaccine against group B meningococcal disease","volume":"14","author":"Fredriksen JH","year":"1991","unstructured":"Fredriksen JH, Rosenqvist E, Wedege E, . Production, characterization, and control of MenB-vaccine \u2018Folkehelsa\u2019: an outer membrane vesicle vaccine against group B meningococcal disease. NIPH ann 1991; 14: 67\u201379, discussion 79\u201380.","journal-title":"NIPH ann"},{"key":"e_1_2_2_29_2","first-page":"83","article-title":"Bacterial lipopolysacharide extraction with phenol- water and further application of the procedure","volume":"5","author":"Westphal O","year":"1965","unstructured":"Westphal O, Jann JK. Bacterial lipopolysacharide extraction with phenol- water and further application of the procedure. Methods Carbohydr Chem 1965; 5: 83\u201391.","journal-title":"Methods Carbohydr Chem"},{"key":"e_1_2_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390513"},{"key":"e_1_2_2_31_2","first-page":"215","article-title":"Development of a sensitive ELISA for the quantification of human tumour necrosis factor-alpha using 4 polyclonal antibodies","volume":"16","author":"Grebenchtchikov N","year":"2005","unstructured":"Grebenchtchikov N, van der Ven-Jongekrijg J, Pesman GJ, Geurts-Moespot A, van der Meer JW, Sweep FC. Development of a sensitive ELISA for the quantification of human tumour necrosis factor-alpha using 4 polyclonal antibodies. Eur Cytokine Netw 2005; 16: 215\u2013222.","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_2_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.79.5.1497"},{"key":"e_1_2_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22848"},{"key":"e_1_2_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwm057"},{"key":"e_1_2_2_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.4.2257"},{"key":"e_1_2_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9288"},{"key":"e_1_2_2_37_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00015.x"},{"key":"e_1_2_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00005-08"},{"key":"e_1_2_2_39_2","doi-asserted-by":"publisher","DOI":"10.1177\/1753425908095957"},{"key":"e_1_2_2_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-124"},{"key":"e_1_2_2_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060136"},{"key":"e_1_2_2_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200008000-00005"},{"key":"e_1_2_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00237-07"},{"key":"e_1_2_2_44_2","first-page":"L329","article-title":"Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide","volume":"289","author":"Savov JD","year":"2005","unstructured":"Savov JD, Brass DM, Lawson BL, McElvania-Tekippe E, Walker JK, Schwartz DA. Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide. Am J Physiol 2005; 289: L329\u2013L337.","journal-title":"Am J Physiol"},{"key":"e_1_2_2_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6416"},{"key":"e_1_2_2_46_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v23.i12.20"}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425910383999","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425910383999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:59:34Z","timestamp":1777460374000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1753425910383999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,18]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["10.1177\/1753425910383999"],"URL":"https:\/\/doi.org\/10.1177\/1753425910383999","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,18]]}}}