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It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms,<jats:italic>Borrelia garinii<\/jats:italic>(the<jats:italic>Borrelia<\/jats:italic>species most frequently found in NB patients) and<jats:italic>Treponema pallidum<\/jats:italic>, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety<jats:italic>N<\/jats:italic>-palmitoyl-<jats:italic>S<\/jats:italic>-(bis[palmitoyloxy]propyl)cystein (Pam<jats:sub>3<\/jats:sub>C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam<jats:sub>3<\/jats:sub>C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with<jats:italic>B. garinii<\/jats:italic>, this suggests that TLR2 is a major mediator of<jats:italic>Borrelia<\/jats:italic>-induced secretion of CXCL13 from human monocytes.<\/jats:p>","DOI":"10.1128\/iai.01642-06","type":"journal-article","created":{"date-parts":[[2007,6,12]],"date-time":"2007-06-12T02:32:43Z","timestamp":1181615563000},"page":"4351-4356","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":68,"title":["<i>Borrelia garinii<\/i>Induces CXCL13 Production in Human Monocytes through Toll-Like Receptor 2"],"prefix":"10.1128","volume":"75","author":[{"given":"Tobias A.","family":"Rupprecht","sequence":"first","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten J.","family":"Kirschning","sequence":"additional","affiliation":[{"name":"Microbiology, Technical University Munich, Pettenkoferstr. 9a, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Popp","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kastenbauer","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Fingerle","sequence":"additional","affiliation":[{"name":"Microbiology, Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Walter","family":"Pfister","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Koedel","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm732"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.736"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.9.1285"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2741\/1581"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/500467"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh486"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.1.81-90.1993"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.140-147.1999"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.11.1510"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405311200"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2444"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.4049\/jimmunol.163.5.2382","volume":"163","year":"1999","unstructured":"Hirschfeld, M., C. 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