{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:29:04Z","timestamp":1780421344157,"version":"3.54.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"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":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Campylobacter jejuni is the most common bacterial cause of human gastroenteritis and often precedes development of Guillain\u2013Barr\u00e9 syndrome (GBS), a life-threatening paralytic disease. The incorporation of the carbohydrate sialic acid into C. jejuni lipooligosaccharides (LOS) is associated with increased severity of gastroenteritis and with induction of GBS; however, the underlying mechanisms remain completely unknown. In this study, we demonstrate that sialic acids in C. jejuni endotoxin enhance the rapid production of IFN-\u03b2 and TNF-\u03b1 by human dendritic cells (DCs). Using neutralizing Abs and receptors it was shown that these DC-derived cytokines promote the proliferation of human mucosal B cells in a T cell\u2013independent manner. The production of both IFN-\u03b2 and TNF-\u03b1 by DCs in response to LOS requires CD14, and the amplified response of DCs to sialylated C. jejuni LOS is CD14 dependent. Together, these results indicate that sialylation of C. jejuni LOS increases DC activation and promotes subsequent B cell responses through CD14-driven production of IFN-\u03b2 and TNF-\u03b1. This enhanced DC\/B cell response may explain the increased pathogenicity of sialylated C. jejuni and may be key to the initiation of B cell\u2013mediated autoimmunity in GBS.<\/jats:p>","DOI":"10.4049\/jimmunol.1301536","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T03:13:38Z","timestamp":1383016418000},"page":"5636-5645","source":"Crossref","is-referenced-by-count":29,"title":["Sialylation of <i>Campylobacter jejuni<\/i> Endotoxin Promotes Dendritic Cell\u2013Mediated B Cell Responses through CD14-Dependent Production of IFN-\u03b2 and TNF-\u03b1"],"prefix":"10.1093","volume":"191","author":[{"given":"Ruth","family":"Huizinga","sequence":"first","affiliation":[{"name":"Department of Immunology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"van Rijs","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]},{"name":"Department of Neurology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J","family":"Bajramovic","sequence":"additional","affiliation":[{"name":"Unit Alternatives, Biomedical Primate Research Centre , 2288 GJ, Rijswijk,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L","family":"Kuijf","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]},{"name":"Department of Neurology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon D","family":"Laman","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke N","family":"Samsom","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Department of Paediatrics, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart C","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]},{"name":"Department of Neurology, Erasmus MC, University Medical Center Rotterdam , 3000 CA Rotterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,1]]},"reference":[{"key":"2025032406022053300_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408410802636017","article-title":"Immunity to Campylobacter: its role in risk assessment and epidemiology","volume":"35","author":"Havelaar","year":"2009","journal-title":"Crit. 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Immunol."},{"key":"2025032406022053300_r36","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1084\/jem.20011788","article-title":"Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells","volume":"195","author":"Hornef","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025032406022053300_r37","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1074\/jbc.M305790200","article-title":"Response of human pulmonary epithelial cells to lipopolysaccharide involves Toll-like receptor 4 (TLR4)-dependent signaling pathways: evidence for an intracellular compartmentalization of TLR4","volume":"279","author":"Guillot","year":"2004","journal-title":"J. Biol. 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