Fungal cell gigantism during mammalian infection

Oscar Zaragoza, García Rodas Rocío, Joshua D. Nosanchuk, Manuel Cuenca-Estrella, Juan Luis Rodríguez-Tudela, Arturo Casadevall

Research output: Contribution to journalArticle

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 (xm in diameter and capsules resistant to stripping with y-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.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume6
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Fingerprint

Gigantism
Giant Cells
Infection
Cryptococcus neoformans
Capsules
Fungi
Polyploidy
Hyphae
Phagocytes
Cell Size
Agar
Cell Cycle
Stem Cells
Yeasts

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Zaragoza, O., Rocío, G. R., Nosanchuk, J. D., Cuenca-Estrella, M., Rodríguez-Tudela, J. L., & Casadevall, A. (2010). Fungal cell gigantism during mammalian infection. PLoS Pathogens, 6(6). https://doi.org/10.1371/journal.ppat.1000945

Fungal cell gigantism during mammalian infection. / Zaragoza, Oscar; Rocío, García Rodas; Nosanchuk, Joshua D.; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo.

In: PLoS Pathogens, Vol. 6, No. 6, 06.2010.

Research output: Contribution to journalArticle

Zaragoza, O, Rocío, GR, Nosanchuk, JD, Cuenca-Estrella, M, Rodríguez-Tudela, JL & Casadevall, A 2010, 'Fungal cell gigantism during mammalian infection', PLoS Pathogens, vol. 6, no. 6. https://doi.org/10.1371/journal.ppat.1000945
Zaragoza O, Rocío GR, Nosanchuk JD, Cuenca-Estrella M, Rodríguez-Tudela JL, Casadevall A. Fungal cell gigantism during mammalian infection. PLoS Pathogens. 2010 Jun;6(6). https://doi.org/10.1371/journal.ppat.1000945
Zaragoza, Oscar ; Rocío, García Rodas ; Nosanchuk, Joshua D. ; Cuenca-Estrella, Manuel ; Rodríguez-Tudela, Juan Luis ; Casadevall, Arturo. / Fungal cell gigantism during mammalian infection. In: PLoS Pathogens. 2010 ; Vol. 6, No. 6.
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