title: Cryptococcal cell morphology affects host cell interactions and pathogenicity.
abstract: Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 microm. Cell enlargement was observed in vivo, producing cells up to 100 microm. 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 ste3aDelta 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.
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Okagaki
authors.forename: Anna K
authors.initials: AK
authors.lastname: Strain
authors.forename: Judith N
authors.initials: JN
authors.lastname: Nielsen
authors.forename: Caroline
authors.initials: C
authors.lastname: Charlier
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Baltes
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.forename: Françoise
authors.initials: F
authors.lastname: Dromer
authors.forename: Kirsten
authors.initials: K
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000382:microbiology*; D018893:Bronchoalveolar Lavage; D002448:Cell Adhesion; D049109:Cell Proliferation; D003453:Cryptococcosis / Q000378:metabolism* / Q000473:pathology*; D003455:Cryptococcus neoformans / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008172:Lung Diseases, Fungal / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A; D018384:Oxidative Stress; D010587:Phagocytosis; D011003:Ploidies; D012333:RNA, Messenger / Q000235:genetics; D043563:Receptors, Pheromone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D043563:Receptors, Pheromone