Cryptococcal phospholipase B1 is required for intracellular proliferation and control of titan cell morphology during macrophage infection.
Cryptococcal phospholipase B1 is required for intracellular proliferation and control of titan cell morphology during macrophage infection.
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DOI：
10.1128/iai.03104-14
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发表时间：
2015-04
影响因子：
3.1
通讯作者：
May RC
中科院分区：
文献类型：
--
作者：
Evans RJ;Li Z;Hughes WS;Djordjevic JT;Nielsen K;May RC
新型隐球菌是一种机会性真菌病原体，是真菌感染相关死亡的主要原因，特别是在免疫功能低下的宿主中。已知几种毒力因子在隐球菌感染的发病机制中起主要作用，包括磷脂酶B1 （Plb1）。与其他已被充分研究的新隐球菌毒力因子如多糖囊和黑色素的产生相比，Plb1对隐球菌毒力的贡献知之甚少。磷脂酶B1是一种磷脂修饰酶，与隐球菌发病的多个阶段有关，包括肺部感染的开始和持续以及向中枢神经系统的传播，但这些表型的潜在原因尚不清楚。在这里，我们证明了Δplb1敲除菌株新生C.在宿主巨噬细胞内的细胞内生长有深刻的缺陷。这种缺陷是由于增殖减少50%和吞噬体内隐球菌杀伤增加2倍。此外，我们首次表明Δplb1菌株在体外和体内细胞内感染期间经历形态变化，导致非常大的泰坦细胞亚群，这可能是由于减毒突变体无法应对巨噬细胞而产生的。
Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of fungal-infection-related fatalities, especially in immunocompromised hosts. Several virulence factors are known to play a major role in the pathogenesis of cryptococcal infections, including the enzyme phospholipase B1 (Plb1). Compared to other well-studied Cryptococcus neoformans virulence factors such as the polysaccharide capsule and melanin production, very little is known about the contribution of Plb1 to cryptococcal virulence. Phospholipase B1 is a phospholipid-modifying enzyme that has been implicated in multiple stages of cryptococcal pathogenesis, including initiation and persistence of pulmonary infection and dissemination to the central nervous system, but the underlying reason for these phenotypes remains unknown. Here we demonstrate that a Δplb1 knockout strain of C. neoformans has a profound defect in intracellular growth within host macrophages. This defect is due to a combination of a 50% decrease in proliferation and a 2-fold increase in cryptococcal killing within the phagosome. In addition, we show for the first time that the Δplb1 strain undergoes a morphological change during in vitro and in vivo intracellular infection, resulting in a subpopulation of very large titan cells, which may arise as a result of the attenuated mutant's inability to cope within the macrophage.