{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:41:22Z","timestamp":1780605682495,"version":"3.54.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":4917,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1992,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have examined the regulation of complement dependent phagocytosis by macrophage\u2010activating cytokines. Tumor necrosis factor (TNF)\u2010\u03b1 and granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF), but not interferon\u2010\u03b3, interleukin\u20104 or macrophage\u2010CSF, stimulated ingestion of the encapsulated fungal pathogen <jats:italic>Cryptococcus neoformans<\/jats:italic> by resident peritoneal macrophages <jats:italic>in vitro<\/jats:italic>. This was dependent upon opsonization of the yeasts with complement, 72 h of incubation with the cytokines for maximum effect, and the obligate involvement of the macrophage CR3 receptor. TNF\u2010\u03b1 and GM\u2010CSF synergized at low concentrations, resulting in dramatic up\u2010regulation of phagocytosis when compared to either cytokine alone. Supernatants from <jats:italic>C. neoformans<\/jats:italic>\u2010specific T cells also increased macrophage phagocytic efficiency. Finally, the administration ofneutralizing mAb specific for TNF\u2010\u03b1 and GM\u2010CSF increased mortality in <jats:italic>C. neoformans<\/jats:italic>\u2010infected mice, and induced the rapid progression of disease with involvement of the brain and meninges. We conclude that TNF\u2010\u03b1 andGM\u2010CSF are potent regulators of complement\u2010dependent phagocytosis by murine macrophages. Macrophage activation with these two cytokines can completely overcome the anti\u2010phagocytic properties of the virulent yeasts. Our results, therefore, implicate TNF\u2010\u03b1 and GM\u2010CSF as important mediators of resistance to encapsulated pathogens such as <jats:italic>C. neoformans<\/jats:italic> where ingestion of the organism is acritical process in host resistance.<\/jats:p>","DOI":"10.1002\/eji.1830220617","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T18:19:30Z","timestamp":1172773170000},"page":"1447-1454","source":"Crossref","is-referenced-by-count":140,"title":["Cytokine enhancement of complement\u2010dependent phagocytosis by macrophages: synergy of tumor necrosis factor\u2010\u03b1 and granulocyte\u2010macrophage colony\u2010stimulating factor for phagocytosis of <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1002","volume":"22","author":[{"given":"Helen L.","family":"Collins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Bancroft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.3.887"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/154.4.619"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/iai.50.2.598-600.1985","volume":"50","author":"Heidenreich F.","year":"1985","journal-title":"Infect. 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