{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:58:00Z","timestamp":1781909880071,"version":"3.54.5"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Genetic factors that regulate the pathogenesis of pneumonia caused by the fungus<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>are poorly understood. Through a phenotypic strain survey we observed that inbred C3H\/HeN mice develop a significantly greater lung fungal burden than mice of the resistant CBA\/J strain 4 weeks following intratracheal infection with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>ATCC 24067. The aim of the present study was to characterize the inflammatory response of C3H\/HeN mice following<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>pulmonary infection and to identify genetic loci that regulate host defense. Following cryptococcal infection, C3H\/HeN mice demonstrated a Th2 immune response with heightened airway and tissue eosinophilia, goblet cell metaplasia, and significantly higher lung interleukin-5 (IL-5) and IL-13 protein expression relative to CBA\/J mice. Conversely, CBA\/J mice exhibited greater airway and tissue neutrophilia that was associated with significantly higher pulmonary expression of gamma interferon, CXCL10, and IL-17 proteins than C3H\/HeN mice. Using the fungal burden at 4 weeks postinfection as a phenotype, genome-wide quantitative trait locus (QTL) analysis among 435 segregating (C3H\/HeN \u00d7 CBA\/J)F2 (C3HCBAF2) hybrids identified two significant QTLs on chromosomes 1 (<jats:italic>Cnes4<\/jats:italic>) and 9 (<jats:italic>Cnes5<\/jats:italic>) that control susceptibility to cryptococcal pneumonia in an additive manner. Susceptible C3H\/HeN mice carry a resistance allele at<jats:italic>Cnes4<\/jats:italic>and a susceptibility allele at<jats:italic>Cnes5<\/jats:italic>. These studies reveal additional genetic complexity of the host response to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>that is associated with divergent patterns of pulmonary inflammation.<\/jats:p>","DOI":"10.1128\/iai.00417-12","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T05:59:52Z","timestamp":1347947992000},"page":"4167-4176","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Susceptibility to Progressive Cryptococcus neoformans Pulmonary Infection Is Regulated by Loci on Mouse Chromosomes 1 and 9"],"prefix":"10.1128","volume":"80","author":[{"given":"Scott F.","family":"Carroll","sequence":"first","affiliation":[{"name":"Centre for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada"},{"name":"Department of Human Genetics, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin I.","family":"Lafferty","sequence":"additional","affiliation":[{"name":"Centre for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Flaczyk","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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