dc.contributor.author | Zaragoza, Oscar | |
dc.contributor.author | Garcia-Rodas, Rocio | |
dc.contributor.author | Nosanchuk, Joshua D | |
dc.contributor.author | Cuenca-Estrella, Manuel | |
dc.contributor.author | Rodriguez-Tudela, Juan Luis | |
dc.contributor.author | Casadevall, Arturo | |
dc.date.accessioned | 2018-12-13T11:48:46Z | |
dc.date.available | 2018-12-13T11:48:46Z | |
dc.date.issued | 2010-06-17 | |
dc.identifier.citation | PLoS Pathog. 2010;6(6):e1000945. | es_ES |
dc.identifier.issn | 1553-7374 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6846 | |
dc.description.abstract | The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens. | es_ES |
dc.description.sponsorship | O.Z. is supported by grants MPY1025/06, SAF2008-03761 and MPY1142/08 from Ministerio de Ciencia e Innovación and MPY1108/06 from Instituto de Salud Carlos III. A.C. is supported by grants NIH grants AI033774, HL059842, and 5R37AI033142. O.Z. held during part of this work a ‘‘Ramón y Cajal’’ contract.
R.G.R. is supported by a FPI fellowship (reference BES-2009-015913). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cell Proliferation | es_ES |
dc.subject.mesh | Cryptococcosis | es_ES |
dc.subject.mesh | DNA, Fungal | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Fluorescent Antibody Technique | es_ES |
dc.subject.mesh | Gamma Rays | es_ES |
dc.subject.mesh | Gigantism | es_ES |
dc.subject.mesh | Lung Diseases, Fungal | es_ES |
dc.subject.mesh | Macrophages, Alveolar | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred BALB C | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Oxidative Stress | es_ES |
dc.subject.mesh | Phagosomes | es_ES |
dc.subject.mesh | RNA, Messenger | es_ES |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | es_ES |
dc.title | Fungal cell gigantism during mammalian infection | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-4.0 Internacional | * |
dc.identifier.pubmedID | 20585557 | es_ES |
dc.format.volume | 6 | es_ES |
dc.format.number | 6 | es_ES |
dc.format.page | e1000945 | es_ES |
dc.identifier.doi | 10.1371/journal.ppat.1000945 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1553-7374 | es_ES |
dc.relation.publisherversion | https://www.doi.org/10.1371/journal.ppat.1000945 | es_ES |
dc.identifier.journal | PLoS pathogens | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2008-03761 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BES-2009-015913 | es_ES |
dc.rights.accessRights | open access | es_ES |