{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:18:18Z","timestamp":1784809098963,"version":"3.55.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"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":[[2010,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic>is a fungal pathogen causing pulmonary infection and a life-threatening meningoencephalitis in human hosts. The fungus infects the host through inhalation, and thus, the host response in the lung environment is crucial for containment or dissemination of<jats:italic>C. neoformans<\/jats:italic>to other organs. In the lung, alveolar macrophages (AMs) are key players in the host lung immune response, and upon phagocytosis, they can kill<jats:italic>C. neoformans<\/jats:italic>by evoking an effective immune response through a variety of signaling molecules. On the other hand, under conditions not yet fully defined, the fungus is able to survive and proliferate within macrophages. Since the host sphingosine kinase 1 (SK1) regulates many signaling functions of immune cells, particularly in macrophages, in this study we determined the role of SK1 in the host response to<jats:italic>C. neoformans<\/jats:italic>infection. Using wild-type (SK1\/2<jats:sup>+\/+<\/jats:sup>) and SK1-deficient (SK1<jats:sup>\u2212\/\u2212<\/jats:sup>) mice, we found that SK1 is dispensable during infection with a facultative intracellular wild-type<jats:italic>C. neoformans<\/jats:italic>strain. However, SK1 is required to form a host lung granuloma and to prevent brain infection by a<jats:italic>C. neoformans<\/jats:italic>mutant strain lacking the cell wall-associated glycosphingolipid glucosylceramide (\u0394<jats:italic>gcs1<\/jats:italic>), previously characterized as a mutant able to replicate only intracellularly. Specifically, in contrast to those from SK1\/2<jats:sup>+\/+<\/jats:sup>mice, lungs from SK1<jats:sup>\u2212\/\u2212<\/jats:sup>mice have no collagen deposition upon infection with<jats:italic>C. neoformans<\/jats:italic>\u0394<jats:italic>gcs1<\/jats:italic>, and AMs from these mice contain significantly more<jats:italic>C. neoformans<\/jats:italic>cells than AMs from SK1\/2<jats:sup>+\/+<\/jats:sup>mice, suggesting that under conditions in which<jats:italic>C. neoformans<\/jats:italic>is more internalized by AMs, SK1 may become important to control<jats:italic>C. neoformans<\/jats:italic>infection. Indeed, when we induced immunosuppression, a host condition in which wild-type<jats:italic>C. neoformans<\/jats:italic>cells are increasingly found intracellularly, SK1<jats:sup>\u2212\/\u2212<\/jats:sup>survived significantly less than SK1\/2<jats:sup>+\/+<\/jats:sup>mice infected with a facultative intracellular wild-type strain, suggesting that SK1 has an important role in controlling<jats:italic>C. neoformans<\/jats:italic>infection under conditions in which the fungus is predominantly found intracellularly.<\/jats:p>","DOI":"10.1128\/iai.01140-09","type":"journal-article","created":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T04:34:14Z","timestamp":1267504454000},"page":"2342-2352","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Role of Host Sphingosine Kinase 1 in the Lung Response against Cryptococcosis"],"prefix":"10.1128","volume":"78","author":[{"given":"Travis","family":"McQuiston","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Luberto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Del Poeta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology"},{"name":"Department of Microbiology and Immunology"},{"name":"Department of Craniofacial Biology"},{"name":"Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406512200"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0742fje"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801214200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307687200"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28798-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/127.6.694"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2004.03.002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/314425"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.5.1899-1907.1997"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-147-8-2355"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2723-2727.2001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4225-4237.2000"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(01)02035-2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400208"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3359-3365.2004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.09.002"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/386286"},{"key":"e_1_3_2_19_2","first-page":"303","volume":"82","year":"2009","unstructured":"Gellings Lowe, N., J. 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