The Outcome of the Cryptococcus neoformans-Macrophage Interaction Depends on Phagolysosomal Membrane Integrity.
The Outcome of the Cryptococcus neoformans-Macrophage Interaction Depends on Phagolysosomal Membrane Integrity.
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DOI：
10.4049/jimmunol.1700958
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发表时间：
2018-07-15
期刊：
影响因子：
--
通讯作者：
Casadevall A
中科院分区：
文献类型：
--
作者：
De Leon-Rodriguez CM;Rossi DCP;Fu MS;Dragotakes Q;Coelho C;Guerrero Ros I;Caballero B;Nolan SJ;Casadevall A
新型隐球菌（Cryptococcus neoformans，Cn）是一种世界性分布的真菌性病原菌。Cn存在于成熟的吞噬溶酶体中，在那里它经常逃避杀死和复制。Cn诱导吞噬溶酶体膜透化（PMP），但这种现象的机制及其对巨噬细胞活力的影响尚不清楚。在这项研究中，我们使用流式细胞术方法结合细胞活力标记物和LysoTracker来测量J774.16和感染Cn的小鼠骨髓源性巨噬细胞中的PMP。我们的研究结果表明，表现PMP的细胞凋亡标志物呈阳性，表明PMP和凋亡之间的关联。我们研究了磷脂酶B1（PLB 1）在Cn诱导PMP中的作用。感染Cn Δ plb 1突变株的巨噬细胞与感染野生型和PLB 1互补株的巨噬细胞相比，PMP降低，表明该毒力因子的作用机制。巨噬细胞内的囊增大被确定为吞噬溶酶体膜损伤的另一可能机制。巨噬细胞发生凋亡没有保持酸性吞噬溶酶体pH值。诱导PMP与环丙沙星增强巨噬细胞触发裂解胞吐，而非裂解胞吐是常见的，在那些没有PMP。我们的研究结果表明，PMP的调制是决定Cn-巨噬细胞相互作用的结果的关键事件。
Cryptococcus neoformans (Cn) is a fungal pathogen with worldwide distribution. Cn resides within mature phagolysosomes where it often evades killing and replicates. Cn induces phagolysosomal membrane permeabilization (PMP), but the mechanism for this phenomenon and its consequences for macrophage viability are unknown. In this study, we used flow cytometry methodology in combination with cell viability markers and LysoTracker to measure PMP in J774.16 and murine bone marrow derived macrophage infected with Cn. Our results showed that cells manifesting PMP were positive for apoptotic markers, indicating an association between PMP and apoptosis. We investigated the role of phospholipase B1 (PLB1) in Cn-induction of PMP. Macrophages infected with a Cn Δplb1 mutant had reduced PMP compared to those infected with wild-type and PLB1-complemented strains, suggesting a mechanism of action for this virulence factor. Capsular enlargement inside macrophages was identified as an additional likely mechanism for phagolysosomal membrane damage. Macrophages undergoing apoptosis did not maintain an acidic phagolysosomal pH. Induction of PMP with ciprofloxacin enhanced macrophages to trigger lytic exocytosis while non-lytic exocytosis was common in those without PMP. Our results suggest that modulation of PMP is a critical event in determining the outcome of the Cn-macrophage interaction.
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DOI：
10.1186/1756-9966-31-41
发表时间：
2012-05-02
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Hornick JR;Vangveravong S;Spitzer D;Abate C;Berardi F;Goedegebuure P;Mach RH;Hawkins WG
通讯作者：
Hawkins WG
影响因子：
6.4
作者：
Chen, SCA;Muller, M;Sorrell, TC
通讯作者：
Sorrell, TC
影响因子：
3.1
作者：
Feldmesser, M;Kress, Y;Casadevall, A
通讯作者：
Casadevall, A
DOI：
10.1073/pnas.0408592102
发表时间：
2005-01-04
影响因子：
11.1
作者：
Erdal, H;Berndtsson, M;Linder, S
通讯作者：
Linder, S
影响因子：
15.3
作者：
DAMIANI, G;KIYOTAKI, C;BLOOM, BR
通讯作者：
BLOOM, BR