{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T18:08:26Z","timestamp":1779127706478,"version":"3.51.4"},"reference-count":32,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["201809PJT-407084-IT-CFAC-163753"],"award-info":[{"award-number":["201809PJT-407084-IT-CFAC-163753"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fonds de recherche du Qu\u00e9bec \u2013 Sant\u00e9","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Fonds de recherche du Qu\u00e9bec \u2013 Sant\u00e9","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Canadian Rare Diseases Models and Mechanisms Network","award":["RCN-137793"],"award-info":[{"award-number":["RCN-137793"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,8]]},"abstract":"<jats:p>\n                    Human Caspase Recruitment Domain Containing Protein 9 (CARD9) deficiency predisposes to invasive fungal disease, particularly by\n                    <jats:italic>Candida<\/jats:italic>\n                    <jats:italic>spp<\/jats:italic>\n                    . CARD9 deficiency causes chronic central nervous system (CNS) candidiasis. Currently, no animal model recapitulates the chronicity of disease, precluding a better understanding of immunopathogenesis. We established a knock-in mouse homozygous for the recurring p.Y91H mutation (Y91H\n                    <jats:sup>KI<\/jats:sup>\n                    ) and, in parallel to\n                    <jats:italic>\n                      Card9\n                      <jats:sup>-\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice, titrated the intravenous fungal inoculum to the CARD9 genotype to develop a model of chronic invasive candidiasis. Strikingly, CARD9-deficient mice had predominantly CNS involvement, with neurological symptoms appearing late during infection and progressive brain fungal burden in the absence of fulminant sepsis, reflecting the human syndrome. Mononuclear cell aggregation at fungal lesions in the brain correlated with increased MHCII\n                    <jats:sup>+<\/jats:sup>\n                    Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    monocyte numbers at day 1 after infection in WT and Y91H\n                    <jats:sup>KI<\/jats:sup>\n                    mice, but not in\n                    <jats:italic>\n                      Card9\n                      <jats:sup>-\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. At day 4 after infection, neutrophils and additional Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    monocytes were recruited to the CARD9-deficient brain. As in humans, Y91H\n                    <jats:sup>KI<\/jats:sup>\n                    mutant mice demonstrated cerebral multinucleated giant cells and granulomata. Subtle immunologic differences between the hypomorphic (p.Y91H) and null mice were noted, perhaps explaining some of the variability seen in humans. Our work established a disease-recapitulating animal model to specifically decipher chronic CNS candidiasis due to CARD9 deficiency.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.176676","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:00:12Z","timestamp":1748347212000},"source":"Crossref","is-referenced-by-count":1,"title":["A CARD9 deficiency mouse model recapitulates human chronic CNS candidiasis identifying defective monocytic cell responses in immunopathogenesis"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9678-6965","authenticated-orcid":true,"given":"Marija","family":"Landekic","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Angers","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada."},{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongbiao","family":"Li","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Christine","family":"Guiot","sequence":"additional","affiliation":[{"name":"Department of Pathology, McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc-Andr\u00e9","family":"D\u00e9ry","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the 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Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen Bo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada."},{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Gavino","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Luo","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."},{"name":"Department of Human Genetics, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Bernier","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makayla","family":"Kazimerczak-Brunet","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichun","family":"Sun","sequence":"additional","affiliation":[{"name":"Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Center, Montr\u00e9al, Qu\u00e9bec, 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