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This yeast interacts closely with innate immune cells, leading to various fates, including fungal persistence within cells, making possible the dissemination of the yeast cells with monocytes via a Trojan horse strategy. In humans, the natural history of the infection begins with primoinfection during childhood, which is followed by dormancy and, in some individuals, reactivation upon immunosuppression. To address the question of dormancy, we studied\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    infection at the macrophage level (\n                    <jats:italic>in vitro<\/jats:italic>\n                    H99-macrophage interaction) and at the organ level in a murine model of cryptococcosis. We analyzed the diversity of yeast adaptation to the host by characterizing several\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    populations with new assays based on flow cytometry (quantitative flow cytometry, multispectral imaging flow cytometry, sorting), microscopy (dynamic imaging), and gene expression analysis. On the basis of parameters of multiplication and stress response, various populations of yeast cells were observed over time\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Cell sorting allowed the identification of a subpopulation that was less prone to grow under standard conditions than the other populations, with growth enhanced by the addition of serum. Gene expression analysis revealed that this population had specific metabolic characteristics that could reflect dormancy. Our data suggest that dormant yeast cells could exist\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    exhibits a huge plasticity and adaptation to hosts that deserves further study.\n                    <jats:italic>In vitro<\/jats:italic>\n                    generation of dormant cells is now the main challenge to overcome the limited number of yeast cells recovered in our models.\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 sugar-coated unicellular fungus that interacts closely with various cells and organisms, including amoebas, nematodes, and immune cells of mammals. This yeast is able to proliferate and survive in the intracellular environment.\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    causes cryptococcosis, and yeast dormancy in humans has been suggested on the basis of epidemiological evidence obtained years ago. By studying an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of yeast-macrophage interaction and murine models of cryptococcosis, we observed that yeast cells evolve in heterogeneous populations during infection on the basis of global metabolic activity. We compared the growth ability and gene expression of yeast cells belonging to various populations in those two models. We eventually found a population of yeast cells with low metabolism that fit some of the criteria for dormant cells. This paves the way for further characterization of dormancy in\n                    <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/mbio.02580-14","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T08:47:31Z","timestamp":1427878051000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":122,"title":["Cryptococcus neoformans Host Adaptation: Toward Biological Evidence of Dormancy"],"prefix":"10.1128","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-3082","authenticated-orcid":false,"given":"Alexandre","family":"Alanio","sequence":"first","affiliation":[{"name":"Institut Pasteur, Molecular Mycology Unit, Paris, France"},{"name":"CNRS URA3012, Paris, France"},{"name":"Laboratoire de Parasitologie-Mycologie, H\u00f4pital Saint-Louis, Groupe Hospitalier Lariboisi\u00e8re, Saint-Louis, Fernand Widal, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, France"},{"name":"Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Vernel-Pauillac","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Molecular Mycology Unit, Paris, France"},{"name":"CNRS URA3012, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Sturny-Lecl\u00e8re","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Molecular Mycology Unit, Paris, France"},{"name":"CNRS URA3012, 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, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(03)00082-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261418798"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00073-13"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/13693780903451810"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13407"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2011.00871.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01065-08"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2229-2239.2004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2522"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.5.e66"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/65.1.83"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.10.3204-3209.1999"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681219280000511"},{"key":"e_1_3_2_15_2","first-page":"429","volume-title":"Cryptococcus: from human pathogen to model yeast","author":"Dromer F","year":"2010","unstructured":"Dromer F, Casadevall A, Perfect J, Sorrell T. 2010. 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