{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:51:26Z","timestamp":1792662686906,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Group B streptococcus (GBS) is the most important cause of neonatal sepsis, which is mediated in part by TLR2. However, GBS components that potently induce cytokines via TLR2 are largely unknown. We found that GBS strains of the same serotype differ in released factors that activate TLR2. Several lines of genetic and biochemical evidence indicated that lipoteichoic acid (LTA), the most widely studied TLR2 agonist in Gram-positive bacteria, was not essential for TLR2 activation. We thus examined the role of GBS lipoproteins in this process by inactivating two genes essential for bacterial lipoprotein (BLP) maturation: the prolipoprotein diacylglyceryl transferase gene (lgt) and the lipoprotein signal peptidase gene (lsp). We found that Lgt modification of the N-terminal sequence called lipobox was not critical for Lsp cleavage of BLPs. In the absence of lgt and lsp, lipoprotein signal peptides were processed by the type I signal peptidase. Importantly, both the \u0394lgt and the \u0394lsp mutant were impaired in TLR2 activation. In contrast to released factors, fixed \u0394lgt and \u0394lsp GBS cells exhibited normal inflammatory activity indicating that extracellular toxins and cell wall components activate phagocytes through independent pathways. In addition, the \u0394lgt mutant exhibited increased lethality in a model of neonatal GBS sepsis. Notably, LTA comprised little, if any, inflammatory potency when extracted from \u0394lgt GBS. In conclusion, mature BLPs, and not LTA, are the major TLR2 activating factors from GBS and significantly contribute to GBS sepsis.<\/jats:p>","DOI":"10.4049\/jimmunol.180.9.6149","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T19:58:20Z","timestamp":1398283100000},"page":"6149-6158","source":"Crossref","is-referenced-by-count":130,"title":["Lipoproteins Are Critical TLR2 Activating Toxins in Group B Streptococcal Sepsis"],"prefix":"10.1093","volume":"180","author":[{"given":"Philipp","family":"Henneke","sequence":"first","affiliation":[{"name":"Center for Pediatrics and Adolescent Medicine, University Medical Centre Freiburg , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaynoor","family":"Dramsi","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Bacte\u0301ries Pathoge\u0300nes a\u0300 Gram-positif , CNRS URA 2172, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Dipartimento di Patologia e Microbiologia Sperimentale, Universita\u0300 di Messina , Messina ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Chraibi","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Bacte\u0301ries Pathoge\u0300nes a\u0300 Gram-positif , CNRS URA 2172, Paris ,","place":["France"]},{"name":"Institut Cochin, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale Unite\u0301 567, Unite\u0301 Mixte de Recherche, Centre National de la Recherche Scientifique 810, University Descartes , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Bacte\u0301ries Pathoge\u0300nes a\u0300 Gram-positif , CNRS URA 2172, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Theilacker","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Medical Centre Freiburg , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hu\u0308bner","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Medical Centre Freiburg , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Santos-Sierra","sequence":"additional","affiliation":[{"name":"Center for Pediatrics and Adolescent Medicine, University Medical Centre Freiburg , Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Teti","sequence":"additional","affiliation":[{"name":"Dipartimento di Patologia e Microbiologia Sperimentale, Universita\u0300 di Messina , Messina ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas T","family":"Golenbock","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Poyart","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Bacte\u0301ries Pathoge\u0300nes a\u0300 Gram-positif , CNRS URA 2172, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Trieu-Cuot","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Bacte\u0301ries Pathoge\u0300nes a\u0300 Gram-positif , CNRS URA 2172, Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,5,1]]},"reference":[{"key":"2026012809215992300_R1","first-page":"1953","volume-title":"Lancet","year":"2003"},{"key":"2026012809215992300_R2","first-page":"760","volume-title":"Clin. 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