Cryptococcal cell morphology affects host cell interactions and pathogenicity.
Cryptococcal cell morphology affects host cell interactions and pathogenicity.
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DOI：
10.1371/journal.ppat.1000953
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发表时间：
2010-06-17
期刊：
影响因子：
6.7
通讯作者：
Nielsen K
中科院分区：
文献类型：
--
作者：
Okagaki LH;Strain AK;Nielsen JN;Charlier C;Baltes NJ;Chrétien F;Heitman J;Dromer F;Nielsen K
新型隐球菌是一种常见的威胁人类生命的真菌病原体。隐球菌细胞的大小通常为 5 至 10 µm。在体内观察到细胞增大，细胞尺寸达到 100 µm。细胞大小的这些形态变化通过减少宿主单核细胞的吞噬作用、增加对氧化和亚硝化应激的抵抗力以及与中枢神经系统渗透的减少相关来影响致病性。与相反交配类型的菌株共感染可刺激细胞增大，并且 ste3 a Δ 信息素受体突变菌株的细胞增大减少。最后，对这种新型细胞类型中 DNA 含量的分析表明，这些增大的细胞是多倍体、单核，并在体内产生子细胞。这些结果描述了新型隐球菌逃避宿主吞噬作用以允许部分群体在感染早期生存的新机制。因此，形态变化在感染过程中发挥着独特和专门的作用。 新型隐球菌是一种常见的危及生命的机会性人类真菌病原体。新型隐球菌在体外作为芽殖酵母生长，典型的细胞尺寸直径为 5 至 10 µm。早期报告表明，人类感染中存在增大的细胞，但这些细胞的身份及其在毒力中的作用仍然未知。在隐球菌病小鼠吸入模型中也观察到细胞形态的变化。这些增大的“泰坦”细胞占肺部细胞的20%。泰坦细胞的形成被发现受到与信息素传感相关的 G 蛋白偶联受体 (GPCR) 信号转导途径的调节。对泰坦细胞的分析揭示了通过出芽繁殖的单核多倍体细胞，表明细胞生长和有丝分裂的调节发生了变化。泰坦细胞的形成还通过减少宿主单核细胞的吞噬作用来影响宿主与病原体的相互作用，并与宿主内传播的减少相关。这些结果描述了新型隐球菌进行形态发生以逃避宿主吞噬作用的新机制，从而提出了这样的假设：泰坦细胞的形成使得一部分群体得以生存，并在感染过程中发挥独特而专门的作用。
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 ste3 a Δ 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. Cryptococcus neoformans is a common life-threatening opportunistic human fungal pathogen. C. neoformans grows as a budding yeast in vitro with typical cell sizes ranging from 5 to 10 µm in diameter. Early reports suggested the presence of enlarged cells in human infections yet the identity of these cells and their role in virulence remained uncharacterized. Changes in cellular morphology are also observed in the mouse inhalation model of cryptococcosis. These enlarged “titan” cells accounted for 20% of the cells in the lungs. Titan cell formation was found to be regulated by a G-protein coupled receptor (GPCR) signal transduction pathway associated with pheromone sensing. Analysis of titan cells revealed uninucleate, polyploid cells that reproduced by budding, suggesting alterations in the regulation of cell growth and mitosis. Titan cell formation also affected host-pathogen interactions by reducing phagocytosis by host mononuclear cells and was correlated with reduced dissemination within the host. These results describe a novel mechanism by which C. neoformans undergoes morphogenesis to evade host phagocytosis, leading to the hypothesis that titan cell formation allows survival of a subset of the population and plays a unique and specialized role during infection.
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影响因子：
--
作者：
DROMER, F;AUCOUTURIER, P;YENI, P
通讯作者：
YENI, P
Toxoplasma Gondii及其宿主之间的交流：对寄生虫生长，发育，免疫逃避和毒力的影响。
DOI：
10.1111/j.1600-0463.2009.02453.x
发表时间：
2009-05
期刊：
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
影响因子：
--
作者：
Blader IJ;Saeij JP
通讯作者：
Saeij JP
影响因子：
3.1
作者：
Charlier, Caroline;Nielsen, Kirsten;Dromer, Francoise
通讯作者：
Dromer, Francoise
影响因子：
3.6
作者：
Davidson, RC;Nicholls, CB;Heitman, J
通讯作者：
Heitman, J
影响因子：
5.4
作者：
Golden, JW;Linke, J;Schiff, LA
通讯作者：
Schiff, LA