Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity

PLoS Pathogens

Kirsten Nielsen¹  Françoise Dromer²  Laura H. Okagaki³  Nicholas J. Baltes³  Anna K. Strain³  Judith N. Nielsen⁴  Joseph Heitman⁶  Caroline Charlier⁷  Fabrice Chrétien⁷ 

[1] APHP Hôpital Henri Mondor and INSERM U955 team10, Paris, France;Université Paris XII;Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America;Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America;Faculté de médecine;Institut Pasteur, Unité de Mycologie Moléculaire and CNRS URA3012, Paris, France

关键词: Cell formation;    Co-infections;    Cryptococcus neoformans;    Cryptococcus;    Pheromones;    Phagocytosis;    Central nervous system;    Host cells;   

DOI  :  10.1371/journal.ppat.1000953

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. 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 ste3aΔ 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.

【 授权许可】

CC BY