Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS Pathog. 2010 Jun 17;6(6):e1000953. doi: 10.1371/journal.ppat.1000953.
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.
新生隐球菌是一种常见的、危及生命的人类真菌病原体。隐球菌细胞的大小通常为 5 至 10 微米。在体内观察到细胞增大,产生的细胞可达 100 微米。这些细胞大小的形态变化通过降低宿主单核细胞的吞噬作用、增加对氧化和硝化应激的抵抗力,以及与穿透中枢神经系统的能力降低有关,从而影响了致病性。与相反交配型的菌株共同感染会刺激细胞增大,而 ste3aDelta 信息素受体突变株的细胞增大减少。最后,对这种新型细胞类型的 DNA 含量进行分析表明,这些增大的细胞是多倍体、单核的,并在体内产生子细胞。这些结果描述了一种新的机制,通过该机制,新生隐球菌逃避宿主吞噬作用,允许在感染的早期阶段,一部分种群存活下来。因此,形态变化在感染过程中发挥着独特和专门的作用。