{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:22:28Z","timestamp":1787728948129,"version":"build-2784847793"},"reference-count":78,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pulmonary cryptococcosis (PC) in apparently immunocompetent hosts\u2014now the majority of non\u2010HIV cases in Asia\u2014cannot be explained by the traditional opportunistic infection paradigm. Three epidemiological observations point toward occult immune susceptibility: familial clustering documented in multiple case reports and small family studies despite shared environmental exposure, normal routine immunological screening, and species\u2010specific infection patterns between\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    and\n                    <jats:italic>Cryptococcus gattii<\/jats:italic>\n                    . We propose a three\u2010layer framework: upstream genetic variants in pattern recognition, Fc\u03b3 receptor, complement\u2010lectin, and macrophage\u2010regulatory loci (Layer 1) act in concert with intermediate immune phenotypes (Layer 2)\u2014the genetically influenced IL\u201017\/Th17 axis and IgG2 subclass deficiencies, and acquired anti\u2010GM\u2010CSF neutralising autoantibodies\u2014that are proposed to converge on alveolar macrophage dysfunction and defective pulmonary fungal clearance (Layer 3). The three Layer 2 phenotypes differ substantially in evidence strength: anti\u2010GM\u2010CSF autoantibodies have reached clinical validation; IgG2 deficiency remains a mechanistic hypothesis; and IL\u201017\/Th17 deficiency is supported by a single unreplicated study and should be treated as preliminary. This framework is hypothesis\u2010generating, derived from candidate\u2010gene studies, limited immunophenotyping data, and animal models; it has not been validated by genome\u2010wide association studies or prospective functional research, and its clinical value requires confirmation by higher\u2010quality evidence.\n                  <\/jats:p>","DOI":"10.1111\/myc.70210","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:53:21Z","timestamp":1787374401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary Cryptococcosis in Apparently Immunocompetent Hosts: Host Susceptibility, Occult Immunodeficiency and Clinical Implications"],"prefix":"10.1111","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6810-1048","authenticated-orcid":false,"given":"Ran","family":"Ma","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou 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