Role of sphingosine-1-phosphate (S1P) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages
Role of sphingosine-1-phosphate (S1P) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages
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DOI：
10.1099/mic.0.045989-0
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发表时间：
2011-05-01
期刊：
影响因子：
2.8
通讯作者：
Del Poeta, Maurizio
中科院分区：
文献类型：
--
作者：
McQuiston, Travis;Luberto, Chiara;Del Poeta, Maurizio
致病真菌新型隐球菌是免疫功能低下个体发病和死亡的主要原因。人类宿主的感染通过环境暴露后吸入传染性繁殖体发生。在肺中，C。新生儿可以驻留在肺泡空间的细胞外环境中，或者在吞噬作用下，它可以在肺泡巨噬细胞（AM）内存活并在细胞内生长。在以前的研究中，我们发现鞘氨醇激酶1（SK 1）影响了C. AM中的新生儿因此，本研究旨在研究SK 1脂质产物1-磷酸鞘氨醇（SIP）在AM C中的作用。neoformans互动发现细胞外Si P增强了C的吞噬作用。AM的新生儿利用遗传学和药理学的方法，我们进一步表明，胞外SiP发挥其对C. AM通过S1 P受体2（S1 P2）对新生儿进行免疫调节。有趣的是，S1 P2的缺失导致Fc γ受体I（Fc γ RI）、-II和-III的mRNA水平显著降低。总之，我们的数据表明，细胞外S1 P增加抗体介导的吞噬作用，通过S1 P2通过调节吞噬Fc γ受体的表达。
The pathogenic fungus Cryptococcus neoformans is a major cause of morbidity and mortality in immunocompromised individuals. Infection of the human host occurs through inhalation of infectious propagules following environmental exposure. In the lung, C. neoformans can reside in the extracellular environment of the alveolar spaces or, upon phagocytosis, it can survive and grow intracellularly within alveolar macrophages (AMs). In previous studies, we found that sphingosine kinase 1 (SK1) influenced the intracellular residency of C. neoformans within AMs. Therefore, with this study we aimed to examine the role of the SK1 lipid product, sphingosine-1-phosphate (SIP), in the AMs C. neoformans interaction. It was found that extracellular Si P enhances the phagocytosis of C. neoformans by AMs. Using both genetic and pharmacological approaches we further show that extracellular Si P exerts its effect on the phagocytosis of C. neoformans by AMs through S1P receptor 2 (S1P2). Interestingly, loss of S1P2 caused a dramatic decrease in the mRNA levels of Fc gamma receptors I (Fc gamma RI), -II and -III. In conclusion, our data suggest that extracellular S1P increases antibody-mediated phagocytosis through S1P2 by regulating the expression of the phagocytic Fc gamma receptors.