{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:06:53Z","timestamp":1761894413083},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,10,16]],"date-time":"2006-10-16T00:00:00Z","timestamp":1160956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p> <jats:italic>Neisseria meningitidis<\/jats:italic> causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease, is initiated by pattern recognition receptors, among which Toll\u2010like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that <jats:italic>N.\u00a0meningitidis<\/jats:italic> induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis for differential activation of the inflammatory response by two <jats:italic>N.\u00a0meningitidis<\/jats:italic> strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin\u20108 in response to these strains. At the level of signal transduction, the two strains differed substantially in their ability to activate the pathway to nuclear factor <jats:italic>\u03ba<\/jats:italic>B in HEK293\u2010TLR4\/MD2 cells at late, but not early, time points. TLR4 activates two signal transduction pathways: one dependent on the adaptor molecule MyD88 and one independent of MyD88, and these pathways induce distinct patterns of gene expression in response to TLR4 ligands. By using macrophages from TLR2\u2212\/\u2212 mice, we observed that the two strains differed in their ability to activate the TLR4\u2010induced MyD88\u2010independent pathway, but not the MyD88\u2010dependent pathway. This idea was further supported by experiments where either of the two pathways was inhibited and IL\u20108 secretion was measured. These data therefore provide molecular insight into activation of the inflammatory response by <jats:italic>N.\u00a0meningitidis<\/jats:italic>, which is one of the key events in the pathogenesis of meningococcal disease.<\/jats:p>","DOI":"10.1111\/j.1365-3083.2006.01856.x","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T06:12:47Z","timestamp":1161151967000},"page":"646-654","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Two <i>Neisseria meningitidis<\/i> Strains with Different Ability to Stimulate Toll\u2010Like Receptor 4 Through the MyD88\u2010Independent Pathway"],"prefix":"10.1111","volume":"64","author":[{"given":"T. H.","family":"Mogensen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. R.","family":"Paludan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kilian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"\u00d8stergaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,10,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.083001.084359"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1112"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00740-0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1179\/096805100101532261"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.4.1533"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306587200"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.371-380.2004"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1105626"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01180"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35092578"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80086-2"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031023"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni986"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.2940-2950.2005"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207873200"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.6.2120"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.6.2781-2792.1987"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.225"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.621"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324714"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5887"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3339"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1031605100"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3901-3908.2003"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1207"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.9.6042"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7115"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.2.839"}],"container-title":["Scandinavian Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-3083.2006.01856.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-3083.2006.01856.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T01:20:41Z","timestamp":1696900841000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-3083.2006.01856.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,16]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1111\/j.1365-3083.2006.01856.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-3083.2006.01856.x","archive":["Portico"],"relation":{},"ISSN":["0300-9475","1365-3083"],"issn-type":[{"value":"0300-9475","type":"print"},{"value":"1365-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,16]]},"assertion":[{"value":"2006-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}