{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:48:27Z","timestamp":1790218107381,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic> is a major etiological agent of fungal meningoencephalitis. The outcome of cryptococcosis depends on the complex interactions between the pathogenic fungus and host immunity. The understanding of how <jats:italic>C. neoformans<\/jats:italic> manipulates the host immune response through its pathogenic factors remains incomplete. In this study, we defined the roles of a previously uncharacterized protein, Csn1201, in cryptococcal fitness and host immunity. Use of both inhalational and intravenous mouse models demonstrated that the <jats:italic>CSN1201<\/jats:italic> deletion significantly blocked the pulmonary infection and extrapulmonary dissemination of <jats:italic>C. neoformans<\/jats:italic>. The <jats:italic>in vivo<\/jats:italic> hypovirulent phenotype of the <jats:italic>csn1201<\/jats:italic>\u0394 mutant was attributed to a combination of multiple factors, including preferential dendritic cell accumulation, enhanced Th1 and Th17 immune responses, decreased intracellular survival inside macrophages, and attenuated blood\u2013brain barrier transcytosis rather than exclusively to pathogenic fitness. The <jats:italic>csn1201<\/jats:italic>\u0394 mutant exhibited decreased tolerance to various stressors <jats:italic>in vitro<\/jats:italic>, along with reduced capsule production and enhanced cell wall thickness under host-relevant conditions, indicating that the <jats:italic>CSN1201<\/jats:italic> deletion might promote the exposure of cell wall components and thus induce a protective immune response. Taken together, our results strongly support the importance of cryptococcal Csn1201 in pulmonary immune responses and disseminated infection.<\/jats:p>","DOI":"10.3389\/fimmu.2022.890258","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T09:03:10Z","timestamp":1654160590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Cryptococcus neoformans Csn1201 Is Associated With Pulmonary Immune Responses and Disseminated 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