{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:38:14Z","timestamp":1767969494432,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2007,6,27]],"date-time":"2007-06-27T00:00:00Z","timestamp":1182902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Toll\u2010like receptors (TLR) are critical mediators of the immune response to pathogens and human polymorphisms in this gene family regulate inflammatory pathways and are associated with susceptibility to infection. Lipopeptides are present in a wide variety of microbes and stimulate immune responses through TLR1\/2 or TLR2\/6 heterodimers. It is not currently known whether polymorphisms in TLR1 regulate the innate immune response. We stimulated human whole blood with triacylated lipopeptide, a ligand for TLR1\/2 heterodimers, and found substantial inter\u2010individual variation in the immune response. We sequenced the coding region of TLR1 and found a non\u2010synonymous polymorphism, I602S (base pair T1805G), that regulated signalling. In comparison to TLR1_602S, the 602I variant mediated substantially greater basal and lipopeptide\u2010induced NF\u2010\u03baB signalling in transfected HEK293 cells. These signalling differences among TLR1 variants were also found with stimulation by extracts of <jats:italic>Mycobacterium tuberculosis<\/jats:italic>. Furthermore, individuals with the 602II genotype produced substantially more IL\u20106 than those with the 602SS variant in a lipopeptide\u2010stimulated whole\u2010blood cytokine assay. Together, these observations demonstrate that variation in the inflammatory response to bacterial lipopeptides is regulated by a common TLR1 transmembrane domain polymorphism that could potentially impact the innate immune response and clinical susceptibility to a wide spectrum of pathogens.<\/jats:p><jats:p>See accompanying article: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1002\/eji.200737604\">http:\/\/dx.doi.org\/10.1002\/eji.200737604<\/jats:ext-link><\/jats:p>","DOI":"10.1002\/eji.200737034","type":"journal-article","created":{"date-parts":[[2007,6,27]],"date-time":"2007-06-27T10:48:56Z","timestamp":1182941336000},"page":"2280-2289","source":"Crossref","is-referenced-by-count":162,"title":["A common human TLR1 polymorphism regulates the innate immune response to lipopeptides"],"prefix":"10.1002","volume":"37","author":[{"given":"Thomas\u2004R.","family":"Hawn","sequence":"first","affiliation":[]},{"given":"E.\u2004Ann","family":"Misch","sequence":"additional","affiliation":[]},{"given":"Sarah\u2004J.","family":"Dunstan","sequence":"additional","affiliation":[]},{"given":"Guy\u2004E.","family":"Thwaites","sequence":"additional","affiliation":[]},{"given":"Nguyen\u2004T.\u2004N.","family":"Lan","sequence":"additional","affiliation":[]},{"given":"Hoang\u2004T.","family":"Quy","sequence":"additional","affiliation":[]},{"given":"Tran\u2004T.\u2004H.","family":"Chau","sequence":"additional","affiliation":[]},{"given":"Stephanie","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Alex","family":"Nachman","sequence":"additional","affiliation":[]},{"given":"Marta","family":"Janer","sequence":"additional","affiliation":[]},{"given":"Tran\u2004T.","family":"Hien","sequence":"additional","affiliation":[]},{"given":"Jeremy\u2004J.","family":"Farrar","sequence":"additional","affiliation":[]},{"given":"Alan","family":"Aderem","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2007,7,26]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35103577"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.081501.125851"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.2.1.373"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198803243181202"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1988.tb02404.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)06413-6"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2570"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1998.0471"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35021228"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.083001.084359"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04946"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/76048"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1116"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/507907"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409831102"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031220"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501165102"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081902"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2534"},{"key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S1473-3099(05)01308-3","article-title":"Single nucleotide polymorphisms of Toll\u2010like receptors and susceptibility to infectious disease.","volume":"5","author":"Schroder N. 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