Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection.
Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection.
复制标题
旨在对抗细胞内Leishmania感染的溶作质糖胶质的合成类似物。
DOI：
10.1038/s41598-017-09894-8
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发表时间：
2017-08-25
影响因子：
4.6
通讯作者：
Lotter H
中科院分区：
文献类型：
--
作者：
Choy SL;Bernin H;Aiba T;Bifeld E;Lender SC;Mühlenpfordt M;Noll J;Eick J;Marggraff C;Niss H;Roldán NG;Tanaka S;Kitamura M;Fukase K;Clos J;Tannich E;Fujimoto Y;Lotter H
属于利什曼原虫属的细胞内病原体已经开发出有效的策略，使它们能够在宿主免疫细胞内生存。抵消这种免疫逃逸机制的免疫刺激化合物代表了有希望的疾病治疗选择。在这里，我们证明从原生动物寄生虫溶组织内阿米巴 (Eh) 的膜中分离出的脂肽磷酸聚糖 (LPPG)，对主要导致皮肤利什曼病 (CL) 的代表性物种利什曼原虫 (L.) 显示出相当大的免疫刺激作用。治疗导致体外细胞内利什曼原虫数量显着减少，并改善小鼠模型中的 CL。接下来，我们设计并合成了 EhLPPG 所携带的磷脂酰肌醇锚的类似物；其中两种类似物通过诱导促炎细胞因子的产生而再现了天然化合物的抗利什曼原虫活性。此类化合物的使用，无论是单独使用还是作为支持性选择，都可能改善目前对 CL 和由病原体操纵的免疫反应引起的其他疾病的不令人满意的治疗。
Intracellular pathogens belonging to the genus Leishmania have developed effective strategies that enable them to survive within host immune cells. Immunostimulatory compounds that counteract such immunological escape mechanisms represent promising treatment options for diseases. Here, we demonstrate that a lipopeptidephosphoglycan (LPPG) isolated from the membrane of a protozoan parasite, Entamoeba histolytica (Eh), shows considerable immunostimulatory effects targeted against Leishmania (L.) major, a representative species responsible for cutaneous leishmaniasis (CL). Treatment led to a marked reduction in the number of intracellular Leishmania parasites in vitro, and ameliorated CL in a mouse model. We next designed and synthesized analogs of the phosphatidylinositol anchors harbored by EhLPPG; two of these analogs reproduced the anti-leishmanial activity of the native compound by inducing production of pro-inflammatory cytokines. The use of such compounds, either alone or as a supportive option, might improve the currently unsatisfactory treatment of CL and other diseases caused by pathogen-manipulated immune responses.
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影响因子：
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通讯作者：
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