{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:29:26Z","timestamp":1791268166755,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"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":[[2004,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>TNF-\u03b1 is crucial in defense against intracellular microbes. Host immune cells use type 3 complement receptors (CR3) to regulate excess TNF-\u03b1 production during physiological clearance of apoptotic cells. BAD1, a virulence factor of Blastomyces dermatitidis, is displayed on yeast and released during infection. BAD1 binds yeast to macrophages (M\u03c6) via CR3 and CD14 and suppresses TNF-\u03b1, which is required for resistance. We investigated whether blastomyces adhesin 1 (BAD1) exploits host receptors for immune deviation and pathogen survival. Soluble BAD1 rapidly entered M\u03c6, accumulated intracellularly by 10 min after introduction to cells, and trafficked to early and late endosomes. Inhibition of receptor recycling by monodansyl cadaverine blocked association of BAD1 with M\u03c6 and reversed TNF-\u03b1 suppression in vitro. Inhibition of BAD1 uptake with cytochalasin D and FcR-redirected delivery of soluble BAD1 as Ag-Ab complexes or of wild-type yeast opsonized with IgG similarly reversed TNF-\u03b1 suppression. Hence, receptor-mediated entry of BAD1 is requisite in TNF-\u03b1 suppression, and the route of entry is critical. Binding of soluble BAD1 to M\u03c6 of CR3\u2212\/\u2212 and CD14\u2212\/\u2212 mice was reduced to 50 and 33%, respectively, of that in wild-type mice. M\u03c6 of CR3\u2212\/\u2212 and CD14\u2212\/\u2212 mice resisted soluble BAD1 TNF-\u03b1 suppression in vitro, but, in contrast to CR3\u2212\/\u2212 cells, CD14\u2212\/\u2212 cells were still subject to suppression mediated by surface BAD1 on wild-type yeast. CR3\u2212\/\u2212 mice resisted both infection and TNF-\u03b1 suppression in vivo, in contrast to wild-type and CD14\u2212\/\u2212 mice. BAD1 of B. dermatitidis thus co-opts normal host cell physiology by exploiting CR3 to subdue TNF-\u03b1 production and foster pathogen survival.<\/jats:p>","DOI":"10.4049\/jimmunol.173.12.7444","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T18:18:22Z","timestamp":1398017902000},"page":"7444-7453","source":"Crossref","is-referenced-by-count":49,"title":["Exploiting Type 3 Complement Receptor for TNF-\u03b1 Suppression, Immune Evasion, and Progressive Pulmonary Fungal Infection"],"prefix":"10.1093","volume":"173","author":[{"given":"T Tristan","family":"Brandhorst","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Wu\u0308thrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bea","family":"Finkel-Jimenez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Warner","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Department of Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Department of 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":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,12,15]]},"reference":[{"key":"2026020212100323100_R1","first-page":"695","volume-title":"Am. 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