Trypanosomatid and fungal glycolipids and sphingolipids as infectivity factors and potential targets for development of new therapeutic strategies
Trypanosomatid and fungal glycolipids and sphingolipids as infectivity factors and potential targets for development of new therapeutic strategies
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DOI：
10.1016/j.bbagen.2007.09.009
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发表时间：
2008-03-01
影响因子：
3
通讯作者：
Takahashi, Hello K.
中科院分区：
文献类型：
--
作者：
Suzuki, Erika;Tanaka, Arneria K.;Takahashi, Hello K.
来自不同人类病原体的几种（糖）（鞘）脂已被表征，并且这些分子中的许多经常参与宿主-病原体相互作用。例如，在亚马逊利什曼原虫（Leishmania）中，无鞭毛体存在于其表面鞘糖脂（GSL）上，其结构为Gal β 1-3Gal α，其被巨噬细胞的30 kDa受体识别。此外，其他利什曼原虫属物种，如硕大利什曼原虫（Leishmania（Leishmania）major）和巴西利什曼原虫（Leishmania（Viannia）braziliensis呈现参与利什曼原虫-巨噬细胞相互作用的糖基肌醇磷脂（GIPL）。值得一提的是，这些抗原在哺乳动物细胞中不表达。利什曼原虫前鞭毛体也提出肌醇磷酸神经酰胺（IPC），一种独特的鞘脂特征的真菌和植物。据观察，IPC合成对于寄生虫分裂至关重要，因为IPC合成酶抑制剂Aureobasidin A显着抑制前鞭毛体和无鞭毛体的生长。最近，还证明GIPL、IPC和甾醇优先存在于4 ℃下对Triton X-100具有抗性的寄生虫膜微区中。通过用甲基-β-环糊精孵育寄生虫来破坏这些微结构域显著抑制利什曼原虫对巨噬细胞的感染性。其他病原体，如真菌，也存在独特的糖脂，其可能对真菌发育和/或疾病建立具有重要作用。结合这些结果，本文将讨论不同病原体的（糖）（鞘）脂的不同生物学作用。(c)2007 Elsevier B. V.保留所有权利。
Several (glyco)(sphingo)lipids from different human pathogens have been characterized, and frequently many of these molecules are participating in host-pathogen interaction. In Leishmania (Leishmania) amazonensis, for example, amastigotes present on their surface glycosphingolipids (GSLs) with the structure Gal beta 1-3Gal alpha, which is recognized by 30 kDa receptor of macrophages. Furthermore, other Leishmania species, such as Leishmania (Leishmania) major and Leishmania (Viannia) braziliensis present glycosylinositolphospholipids (GIPLs) which are involved in Leishmania-macrophage interaction. It is worth to mention that these antigens are not expressed in mammalian cells. Leishmania promastigotes also present inositol phosphorylceramide (IPC), a unique sphingolipid characteristic of fungi and plants. It was observed that IPC synthesis is essential for parasite division, since Aureobasidin A, an inhibitor of IPC synthase, inhibited significantly promastigote and amastigote growths. Recently, it was also demonstrated that GIPLs, IPC and sterols are preferentially present in the parasite membrane microdomains resistant to Triton X-100 at 4 degrees C. The disruption of these microdomains by incubating parasites with methyl-beta-cyclodextrin inhibited significantly macrophage infectivity by Leishmania. Other pathogens, such as fungi, also present unique glycolipids which may have an important role for the fungal development and/or disease establishment. Taking together these results, this review will discuss different biological roles for (glyco)(sphingo)lipids of different pathogens. (c) 2007 Elsevier B.V. All rights reserved.