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In the present study, we demonstrate that cell-surface \u03b2-glucan components of Pneumocystis (PCBG) stimulate human dendritic cells (DCs) to secrete IL-23 and IL-6. These cytokines are well established to stimulate a T helper\u201317 (Th17) phenotype. Accordingly, we further observe that PCBG-stimulated human DCs interact with lymphocytes to drive the secretion of IL-17 and IL-22, both Th17-produced cytokines. The activation of DCs was shown to involve the dectin-1 receptor with a downstream activation of the Syk kinase and subsequent translocation of both the canonical and noncanonical components of the NF-\u03baB transcription factor family. Finally, we demonstrate that glycosphingolipid-rich microdomains of the plasma membrane participate in the activation of DCs by PCBG through the accumulation of lactosylceramide at the cell surface during stimulation with PCBG. These data strongly support the idea that the \u03b2-glucan surface components of Pneumocystis drive the activation of the IL-23\/IL-17 axis during this infection, through a glycosphingolipid-initiated mechanism.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0159oc","type":"journal-article","created":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T00:25:43Z","timestamp":1329438343000},"page":"50-59","source":"Crossref","is-referenced-by-count":38,"title":["Glycosphingolipids Mediate\n                    <i>Pneumocystis<\/i>\n                    Cell Wall \u03b2-Glucan Activation of the IL-23\/IL-17 Axis in Human Dendritic Cells"],"prefix":"10.1093","volume":"47","author":[{"given":"Eva M.","family":"Carmona","sequence":"first","affiliation":[{"name":"Thoracic Diseases Research Unit and Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore 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Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman-Deep","family":"Singh","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit and Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Pagano","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit and Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Limper","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit and Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic and Foundation, Rochester, 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