{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T03:11:27Z","timestamp":1771989087172,"version":"3.50.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"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":[[2007,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The brain represents a significant barrier for protective immune responses in both infectious disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-\u03b3 knockout mice and IFN-\u03b3R knockout mice demonstrated that IFN-\u03b3 was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40\/IL-2. Interestingly, while peripheral IFN-\u03b3 production and microglial cell activation were observed early after treatment, negligible IFN-\u03b3 was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-\u03b3 is essential for this effect.<\/jats:p>","DOI":"10.4049\/jimmunol.178.9.5753","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:04:28Z","timestamp":1397862268000},"page":"5753-5761","source":"Crossref","is-referenced-by-count":51,"title":["Protection from Direct Cerebral <i>Cryptococcus<\/i> Infection by Interferon-\u03b3-Dependent Activation of Microglial Cells"],"prefix":"10.1093","volume":"178","author":[{"given":"Qing","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Blood and Marrow Transplantation, Cancer Center and Department of Pediatrics, MMC 109, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth A","family":"Gault","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Nevada , Reno, Reno, NV 89557"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R","family":"Kozel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Nevada , Reno, Reno, NV 89557"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Nevada , Reno, Reno, NV 89557"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,5,1]]},"reference":[{"key":"2025032702490074400_R1","first-page":"933","volume-title":"Ann. 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