Fungal cell gigantism during mammalian infection.
Fungal cell gigantism during mammalian infection.
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DOI：
10.1371/journal.ppat.1000945
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发表时间：
2010-06-17
期刊：
影响因子：
6.7
通讯作者：
Casadevall A
中科院分区：
文献类型：
--
作者：
Zaragoza O;García-Rodas R;Nosanchuk JD;Cuenca-Estrella M;Rodríguez-Tudela JL;Casadevall A
真菌病原体与宿主之间的相互作用经常导致形态变化，如菌丝形成。被包裹的病原性真菌新型隐球菌不被认为是二型真菌，并且主要在宿主组织中作为圆形酵母细胞被发现。然而，有一个特定的形态学变化与隐球菌感染，涉及胶囊体积的增加。我们现在报道另一种形态学变化，即在组织中形成巨大的细胞。本文报道了从感染小鼠中分离的巨细胞的表型特征和与巨细胞形成相关的细胞变化。C.小鼠中的新形虫感染导致巨细胞的出现，其细胞体直径达30 µm，并且胶囊对γ辐射和有机溶剂的剥离具有抗性。巨细胞的比例范围从10%到80%的总肺真菌负荷，这取决于感染时间，个体小鼠，并与免疫反应的类型相关。当放置在琼脂上时，巨细胞出芽产生小子细胞，这些小子细胞以20-50 m/h的速度穿过母细胞的囊。巨细胞的尺寸接近那些在体内观察到在体外培养后，在基本培养基中长时间培养，是最古老的文化，这表明巨细胞的形成是一个老化依赖的现象。从小鼠中回收的巨细胞显示出多倍性，这表明了一种机制，即巨噬细胞是由细胞周期进展而不是细胞分裂引起的。巨细胞的形成依赖于cAMP，而不是Ras 1。实时成像显示巨细胞参与，但没有被吞噬细胞吞噬。我们描述了一个显着的新策略C。新形式的真菌通过扩大细胞大小来逃避免疫反应，并表明寄生虫病是由没有分裂的复制引起的，这种现象也可能发生在其他真菌病原体中。在这篇文章中，我们描述了由人类真菌病原体新型隐球菌感染过程中形成的巨细胞，涉及约900倍的体积增加相比，在体外生长的酵母细胞。这种转变是一个戏剧性的转变，被认为在感染过程中会产生重要的后果。本文报道了这些细胞的表型特征和巨细胞形成与多倍性之间的关系，这表明，巨细胞化是通过细胞持续生长和DNA复制而不分裂来实现的。在感染过程中，我们观察到受感染小鼠肺中巨细胞的比例与动物引起的炎症反应之间存在负相关性。总之，我们的结果表明，在感染过程中，C。新生菌形成巨细胞，这可能与真菌在宿主体内长时间存活有关，特别是在慢性和无症状感染期间。寄生能力是真菌致病机制中一个重要的新方面，它为病原体提供了逃避宿主防御的能力。我们认为，向寄生性的转变可能对宿主-病原体相互作用产生深远的影响，包括促进宿主中真菌的持久性，这可能转化为潜伏期和疾病复发。
The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 µm in diameter and capsules resistant to stripping with γ-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20–50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens. In this article we describe the formation of giant cells by the human fungal pathogen Cryptococcus neoformans during infection, involving an approximately 900-fold increase in volume compared to that of yeast cells grown in vitro. This switch to gigantism is a dramatic transition that is posited to have important consequences during infection. The paper reports the phenotypic characterization of these cells and the relationship between giant cell formation and polyploidy which suggests that gigantism is achieved by continued cell growth and DNA replication without fission. During infection, we observed an inverse correlation between the proportion of giant cells in the lung of infected mice and the inflammatory response elicited by the animals. In conclusion, our results indicate that during infection, C. neoformans forms giant cells, which might be implicated in fungal survival in the host during long time periods, especially during chronic and asymptomatic infection. The capacity for gigantism is an important new facet in fungal pathogenesis that provides the pathogen with the ability to escape host defences. We propose that the transition to gigantism can have profound consequences for the host-pathogen interaction including promoting fungal persistence in the host that can translate into latency and disease relapses.
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影响因子：
9.2
作者：
Alvarez, Mauricio;Casadevall, Arturo
通讯作者：
Casadevall, Arturo
影响因子：
3.1
作者：
Feldmesser, M;Kress, Y;Casadevall, A
通讯作者：
Casadevall, A
DOI：
10.1016/s0732-8893(99)00013-9
发表时间：
1999-05-01
影响因子：
2.9
作者：
Bottone, EJ;Horga, M;Abrams, J
通讯作者：
Abrams, J
影响因子：
4.3
作者：
Grebien, F;Dolznig, H;Mullner, EW
通讯作者：
Mullner, EW
影响因子：
3
作者：
Garcia-Rivera, J;Eisenman, HC;Casadevall, A
通讯作者：
Casadevall, A