{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T09:07:34Z","timestamp":1770282454807,"version":"3.49.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"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":[[2001,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The WI-1 adhesin is indispensable for pathogenicity of Blastomyces dermatitidis and is thought to promote pulmonary infection by fixing yeast to lung tissue and cells. Recent findings suggest that WI-1 confers pathogenicity by mechanisms in addition to adherence. Here, we investigated whether WI-1 modulates host immunity by altering production of pro-inflammatory cytokines. Production of TNF-\u03b1 in lung alveolar fluids of mice infected with B. dermatitidis was severalfold higher for WI-1 knockout yeast compared with wild-type yeast, and in vitro coculture of unseparated lung cells with these isogenic yeast disclosed similar differences. Upon coculture with purified macrophages and neutrophils, wild-type yeast blocked TNF-\u03b1 production, yet WI-1 knockout yeast stimulated production. Coating knockout yeast with purified WI-1 converted them from stimulating TNF-\u03b1 production to inhibiting production. Addition of purified WI-1 into stimulated phagocyte cultures led to concentration-dependent inhibition of TNF-\u03b1 production. Neutralization of TNF-\u03b1 in vivo exacerbated experimental pulmonary infection, particularly for the nonpathogenic WI-1 knockout yeast. Inducing increased TNF-\u03b1 levels in the lung by adenovirus-vectored gene therapy controlled infection with wild-type yeast. Thus, the WI-1 adhesin on yeast modulates host immunity through blocking TNF-\u03b1 production by phagocytes, which fosters progression of pulmonary infection.<\/jats:p>","DOI":"10.4049\/jimmunol.166.4.2665","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:56:08Z","timestamp":1398034568000},"page":"2665-2673","source":"Crossref","is-referenced-by-count":57,"title":["The WI-1 Adhesin Blocks Phagocyte TNF-\u03b1 Production, Imparting Pathogenicity on\n                    <i>Blastomyces dermatitidis<\/i>"],"prefix":"10.1093","volume":"166","author":[{"given":"Bea","family":"Finkel-Jimenez","sequence":"first","affiliation":[{"name":"Pediatrics, University of Wisconsin Hospital and Clinics , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Wu\u0308thrich","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Wisconsin Hospital and Clinics , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Brandhorst","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Wisconsin Hospital and Clinics , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce S","family":"Klein","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Wisconsin Hospital and Clinics , Madison, WI"},{"name":"Internal Medicine, University of Wisconsin Hospital and Clinics , Madison, WI"},{"name":"Medical Microbiology and Immunology, University of Wisconsin Hospital and Clinics , Madison, WI"},{"name":"Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,2,15]]},"reference":[{"key":"2026020209150514400_R1","first-page":"695","volume-title":"Am. 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