{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:51Z","timestamp":1791296991646,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2011,8,9]],"date-time":"2011-08-09T00:00:00Z","timestamp":1312848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":["mBio"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cryptococcosis is a multifaceted fungal infection with variable clinical presentation and outcome. As in many infectious diseases, this variability is commonly assigned to host factors. To investigate whether the diversity of\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            clinical (ClinCn) isolates influences the interaction with host cells and the clinical outcome, we developed and validated new quantitative assays using flow cytometry and J774 macrophages. The phenotype of ClinCn-macrophage interactions was determined for 54 ClinCn isolates recovered from cerebrospinal fluids (CSF) from 54 unrelated patients, based on phagocytic index (PI) and 2-h and 48-h intracellular proliferation indexes (IPH2 and IPH48, respectively). Their phenotypes were highly variable. Isolates harboring low PI\/low IPH2 and high PI\/high IPH2 values were associated with nonsterilization of CSF at week 2 and death at month 3, respectively. A subset of 9 ClinCn isolates with different phenotypes exhibited variable virulence in mice and displayed intramacrophagic expression levels of the\n            <jats:italic>LAC1<\/jats:italic>\n            ,\n            <jats:italic>APP1<\/jats:italic>\n            ,\n            <jats:italic>VAD1<\/jats:italic>\n            ,\n            <jats:italic>IPC1<\/jats:italic>\n            ,\n            <jats:italic>PLB1<\/jats:italic>\n            , and\n            <jats:italic>COX1<\/jats:italic>\n            genes that were highly variable among the isolates and correlated with IPH48. Variation in the expression of virulence factors is thus shown here to depend on not only experimental conditions but also fungal background. These results suggest that, in addition to host factors, the patient\u2019s outcome can be related to fungal determinants. Deciphering the molecular events involved in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            fate inside host cells is crucial for our understanding of cryptococcosis pathogenesis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            is a life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis\/year, predominantly in HIV-infected patients. The diversity of infecting isolates is well established, as is the importance of the host factors. Interaction with macrophages is a major step in cryptococcosis pathogenesis. How the diversity of clinical isolates influences macrophages\u2019 interactions and impacts cryptococcosis outcome in humans remains to be elucidated. Using new assays, we uncovered how yeast-macrophage interactions were highly variable among clinical isolates and found an association between specific behaviors and cryptococcosis outcome. In addition, gene expression of some virulence factors and intracellular proliferation were correlated. While many studies have established that virulence factors can be differentially expressed as a function of experimental conditions, our study demonstrates that, under the same experimental conditions, clinical isolates behaved differently, a diversity that could participate in the variable outcome of infection in humans.\n          <\/jats:p>","DOI":"10.1128\/mbio.00158-11","type":"journal-article","created":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T02:34:54Z","timestamp":1312943694000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":104,"title":["Dynamics of Cryptococcus neoformans-Macrophage Interactions Reveal that Fungal Background Influences Outcome during Cryptococcal Meningoencephalitis in Humans"],"prefix":"10.1128","volume":"2","author":[{"given":"Alexandre","family":"Alanio","sequence":"first","affiliation":[{"name":"Institut Pasteur, Molecular Mycology Unit, Paris, France"},{"name":"CNRS URA3012, Institut Pasteur, Paris, France"},{"name":"Service de Maladies Infectieuses et Tropicales, H\u00f4pital Necker-Enfants Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Desnos-Ollivier","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Molecular Mycology Unit, Paris, France"},{"name":"CNRS URA3012, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Dromer","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Molecular Mycology Unit, Paris, France"},{"name":"CNRS URA3012, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/9781555818241","volume-title":"Cryptococcus neoformans, p.","author":"Casadevall A","year":"1998","unstructured":"CasadevallA PerfectJ . 1998. 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