Cryptococcal cell morphology affects host cell interactions and pathogenicity.
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.
Okagaki
Laura H
LH
Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America.
Strain
Anna K
AK
Nielsen
Judith N
JN
Charlier
Caroline
C
Baltes
Nicholas J
NJ
Chrétien
Fabrice
F
Heitman
Joseph
J
Dromer
Françoise
F
Nielsen
Kirsten
K
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
D012333:RNA, Messenger; D043563:Receptors, Pheromone