{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:45:57Z","timestamp":1787863557698,"version":"build-2784847793"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Rare Diseases: Models and Mechanisms Network (SQ)","award":["159588"],"award-info":[{"award-number":["159588"]}]},{"name":"Canadian Institutes of Health Research","award":["159588"],"award-info":[{"award-number":["159588"]}]},{"name":"J.T. Costello Memorial Bequest (SQ)","award":["159588"],"award-info":[{"award-number":["159588"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>The ubiquitous soil-associated fungus Cryptococcus neoformans causes pneumonia that may progress to fatal meningitis. Recognition of fungal cell walls by C-type lectin receptors (CLRs) has been shown to trigger the host immune response. Caspase recruitment domain-containing protein 9 (Card9) is an intracellular adaptor that is downstream of several CLRs. Experimental studies have implicated Card9 in host resistance against C. neoformans; however, the mechanisms that are associated with susceptibility to progressive infection are not well defined. To further characterize the role of Card9 in cryptococcal infection, Card9em1Sq mutant mice that lack exon 2 of the Card9 gene on the Balb\/c genetic background were created using CRISPR-Cas9 genome editing technology and intratracheally infected with C. neoformans 52D. Card9em1Sq mice had significantly higher lung and brain fungal burdens and shorter survival after C. neoformans 52D infection. Susceptibility of Card9em1Sq mice was associated with lower pulmonary cytokine and chemokine production, as well as reduced numbers of CD4+ lymphocytes, neutrophils, monocytes, and dendritic cells in the lungs. Histological analysis and intracellular cytokine staining of CD4+ T cells demonstrated a Th2 pattern of immunity in Card9em1Sq mice. These findings demonstrate that Card9 broadly regulates the host inflammatory and immune response to experimental pulmonary infection with a moderately virulent strain of C. neoformans.<\/jats:p>","DOI":"10.3390\/jof10060434","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T08:06:06Z","timestamp":1718784366000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Card9 Broadly Regulates Host Immunity against Experimental Pulmonary Cryptococcus neoformans 52D Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Isabelle","family":"Angers","sequence":"first","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2161-715X","authenticated-orcid":false,"given":"Wided","family":"Akik","sequence":"additional","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Meakins-Christie Laboratories, Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irah L.","family":"King","sequence":"additional","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Meakins-Christie Laboratories, Department of Microbiology and Immunology, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry C.","family":"Lands","sequence":"additional","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Meakins-Christie Laboratories, Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman T.","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41572-023-00472-z","article-title":"Cryptococcal meningitis","volume":"9","author":"Tugume","year":"2023","journal-title":"Nat. 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