{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:57:17Z","timestamp":1791287837311,"version":"4.3.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"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":[[2012,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Experimental pulmonary Cryptococcus neoformans infection in BALB\/c mice is associated with polarized Th2-type cytokine production, alternative macrophage activation, and severe bronchopneumonia. In contrast, pulmonary infection with a C. neoformans strain that secretes IFN-\u03b3, H99\u03b3, elicits Th1-type cytokine production and classical macrophage activation. Additionally, mice infected with H99\u03b3 resolve the acute infection and are subsequently protected against challenge with wild-type C. neoformans. The present study characterizes macrophage activation during the protective response to wild-type C. neoformans in mice previously immunized with H99\u03b3. We observed increased pulmonary Th1-type cytokine production in lung homogenates and classical macrophage activation as evidenced by enhanced expression of inducible NO synthase in the lungs of H99\u03b3-immunized mice compared with mice given a nonprotective immunization with heat-killed C. neoformans (HKCn). Furthermore, macrophages isolated from H99\u03b3-immunized mice on day 7 postchallenge and cultured in vitro were fungistatic against C. neoformans, whereas cryptococcal growth was uncontrolled within macrophages from HKCn-immunized mice. Th2-type cytokine production and induction of alternatively activated macrophages were also observed in lungs of HKCn-immunized mice during rechallenge. Gene expression arrays showed that classical macrophage activation during challenge infection in H99\u03b3-immunized mice was associated with induction of the transcription factor STAT1 and its downstream targets IFN regulatory factor-1, suppressor of cytokine signaling-1, CXCL9, and CXCL10. These studies demonstrate that protective responses to C. neoformans challenge in immunized mice include classical macrophage activation and enhanced macrophage fungistasis of C. neoformans yeasts. Finally, the classical activation phenotype of protective anticryptococcal macrophages is likely mediated via STAT1 signal transduction pathways.<\/jats:p>","DOI":"10.4049\/jimmunol.1103455","type":"journal-article","created":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T10:43:49Z","timestamp":1347705829000},"page":"4060-4068","source":"Crossref","is-referenced-by-count":90,"title":["Protective Immunity against Pulmonary Cryptococcosis Is Associated with STAT1-Mediated Classical Macrophage Activation"],"prefix":"10.1093","volume":"189","author":[{"given":"Sarah E","family":"Hardison","sequence":"first","affiliation":[{"name":"Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249; and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249; and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattie L","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249; and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camaron R","family":"Hole","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249; and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249; and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Floyd L","family":"Wormley","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249; and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,10,15]]},"reference":[{"key":"2025032409294845000_r1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","article-title":"Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\/AIDS","volume":"23","author":"Park","year":"2009","journal-title":"AIDS"},{"key":"2025032409294845000_r2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1128\/CMR.8.4.515","article-title":"Cryptococcosis in the era of AIDS: 100 years after the discovery of Cryptococcus neoformans","volume":"8","author":"Mitchell","year":"1995","journal-title":"Clin. 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