{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:00:12Z","timestamp":1761292812835},"reference-count":56,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Haemophilus ducreyi<\/jats:named-content>causes chancroid, a genital ulcer disease. In human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. The immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the<jats:sc>l<\/jats:sc>-tryptophan-kynurenine metabolic pathway. Tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting T cell proliferation, inducing T cell apoptosis, and promoting the expansion of FOXP3<jats:sup>+<\/jats:sup>regulatory T (Treg) cells. We previously found that FOXP3<jats:sup>+<\/jats:sup>Treg cells are enriched in experimental lesions and that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. ducreyi<\/jats:named-content>induced IDO transcription in dendritic cells (DC) derived from blood of infected volunteers who developed pustules. Here, we showed that enzymatically active IDO was induced in DC by<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. ducreyi<\/jats:named-content>. Neutralizing antibodies against interferon alpha\/beta receptor 2 chain (IFNAR2) and tumor necrosis factor alpha (TNF-\u03b1) inhibited IDO induction. Inhibitors of the mitogen-activated protein kinase (MAPK) p38 and nuclear factor-\u03baB (NF-\u03baB) also inhibited IDO expression. Neither bacterial contact with nor uptake by DC was required for IDO activation.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. ducreyi<\/jats:named-content>culture supernatant and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. ducreyi<\/jats:named-content>lipooligosaccharides (LOS) induced IDO expression, which required type I interferons, TNF-\u03b1, and the three MAPK (p38, c-Jun N-terminal kinase, and extracellular signal regulated kinase) and NF-\u03baB pathways. In addition, LOS-induced IFN-\u03b2 activated the JAK-STAT pathway. Blocking the LOS\/Toll-like receptor 4 (TLR4) signaling pathway greatly reduced<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. ducreyi<\/jats:named-content>-induced IDO production. These findings indicate that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">H. ducreyi<\/jats:named-content>-induced IDO expression in DC is largely mediated by LOS via type I interferon- and TNF-\u03b1-dependent mechanisms and the MAPK, NF-\u03baB, and JAK-STAT pathways.<\/jats:p>","DOI":"10.1128\/iai.05021-11","type":"journal-article","created":{"date-parts":[[2011,5,17]],"date-time":"2011-05-17T01:57:30Z","timestamp":1305597450000},"page":"3338-3347","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Haemophilus ducreyi Lipooligosaccharides Induce Expression of the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase via Type I Interferons and Tumor Necrosis Factor Alpha in Human Dendritic Cells"],"prefix":"10.1128","volume":"79","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Departments of Medicine, Indiana University, School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry P.","family":"Katz","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Indiana University, School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley M.","family":"Spinola","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Indiana University, School of Medicine, Indianapolis, Indiana 46202"},{"name":"Microbiology and Immunology, Indiana University, School of Medicine, Indianapolis, Indiana 46202"},{"name":"Pathology and Laboratory Medicine, Indiana University, School of Medicine, Indianapolis, Indiana 46202"},{"name":"Center for Immunobiology, Indiana University, School of Medicine, Indianapolis, Indiana 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.04.007"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900986"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh271"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1999.0661"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/588001"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00702-07"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/013953-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2549-2557.2001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.06.001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-0979"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.8.2601-2608.1991"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.8.5396"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-191197"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999000312306"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-006700"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00031-09"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000632"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020121"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/jb\/mvj072","article-title":"The signal transducer and activator of transcription 1\u03b1 and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: involvement of p38 mitogen-activated protein kinase and nuclear factor-\u03baB pathways, and synergistic effect of several proinflammatory cytokines","volume":"139","author":"Fujigaki H.","year":"2006","unstructured":"FujigakiH. . 2006. 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