{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:41:45Z","timestamp":1779097305085,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2002,6,1]],"date-time":"2002-06-01T00:00:00Z","timestamp":1022889600000},"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":[[2002,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated how BAD1, an adhesin and virulence factor of Blastomyces dermatitidis, suppresses phagocyte proinflammatory responses. Wild-type yeast cocultured with murine neutrophils or macrophages prompted release of a soluble factor into conditioned supernatant that abolished TNF-\u03b1 production in response to the fungus; isogenic, attenuated BAD1 knockout yeast did not have this effect. Phagocytes released 4- to 5-fold more TGF-\u03b2 in vitro in response to wild-type yeast vs BAD1 knockout yeast. Treatment of inhibitory, conditioned supernatant with anti-TGF-\u03b2 mAb neutralized detectable TGF-\u03b2 and restored phagocyte TNF-\u03b1 production. Similarly, addition of anti-TGF-\u03b2 mAb into cultures of phagocytes and wild-type yeast reversed BAD1 inhibition of TNF-\u03b1 production. Conversely, TGF-\u03b2 treatment of phagocytes cultured with knockout yeast suppressed TNF-\u03b1 production. Hence, TGF-\u03b2 mediates BAD1 suppression of TNF-\u03b1 by wild-type B. dermatitidis cultured in vitro with phagocytes. In contrast to these findings, neutralization of elevated TGF-\u03b2 levels during experimental pulmonary blastomycosis did not restore BAD1-suppressed TNF-\u03b1 levels in the lung or ameliorate disease. Soluble BAD1 was found to accumulate in the alveoli of infected mice at levels that suppressed TNF-\u03b1 production by phagocytes. However, in contrast to yeast cell surface BAD1, which induced TGF-\u03b2, soluble BAD1 failed to do so and TNF-\u03b1 suppression mediated by soluble BAD1 was unaffected by neutralization of TGF-\u03b2. Thus, BAD1 of B. dermatitidis induces suppression of TNF-\u03b1 and progressive infection by both TGF-\u03b2-dependent and -independent mechanisms.<\/jats:p>","DOI":"10.4049\/jimmunol.168.11.5746","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T22:43:29Z","timestamp":1398120209000},"page":"5746-5755","source":"Crossref","is-referenced-by-count":75,"title":["BAD1, an Essential Virulence Factor of\n                    <i>Blastomyces dermatitidis<\/i>\n                    , Suppresses Host TNF-\u03b1 Production Through TGF-\u03b2-Dependent and -Independent Mechanisms"],"prefix":"10.1093","volume":"168","author":[{"given":"Beatriz","family":"Finkel-Jimenez","sequence":"first","affiliation":[{"name":"Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Wu\u0308thrich","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce S","family":"Klein","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,6,1]]},"reference":[{"key":"2026020208172535800_R1","first-page":"695","volume-title":"Am. 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