Cryptococcal cell morphology affects host cell interactions and pathogenicity

Laura H Okagaki-Vraspir, Anna K. Strain, Judith N. Nielsen, Caroline Charlier, Nicholas J. Baltes, Fabrice Chrétien, Joseph H. Heitman, Françoise Dromer, Kirsten Nielsen

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 fim. Cell enlargement was observed in vivo, producing cells up to 100 fim. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aD pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection.

Original languageEnglish (US)
JournalPLoS pathogens
Volume6
Issue number6
DOIs
StatePublished - Jun 2010

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