Toxoplasma gondii uses sulfated proteoglycans for substrate and host cell attachment
Toxoplasma gondii uses sulfated proteoglycans for substrate and host cell attachment
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DOI：
10.1128/iai.68.7.4005-4011.2000
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发表时间：
2000-07-01
影响因子：
3.1
通讯作者：
Sibley, LD
中科院分区：
文献类型：
--
作者：
Carruthers, VB;Håkansson, S;Sibley, LD
刚地弓形虫是一种专性细胞内寄生虫，它能主动侵入多种脊椎动物细胞，然而这种普遍的细胞识别的基础尚不清楚。我们在此证明，它与基质以及宿主细胞的结合部分是通过与硫酸化糖胺聚糖（GAGs）相互作用介导的。添加过量的可溶性GAGs可阻断寄生虫附着在血清包被的玻璃上，从而阻止细胞外寄生虫的滑行运动。同样，过量的可溶性GAGs减少了寄生虫对来自多种谱系的人类宿主细胞的附着，包括单核细胞、成纤维细胞、内皮细胞、上皮细胞和巨噬细胞。用肝素和硫酸乙酰肝素以及硫酸软骨素都观察到了GAGs对寄生虫附着的抑制作用，这表明用于附着的配体能够识别多种GAGs。硫酸化蛋白聚糖识别的重要性进一步得到了以下证据的支持：GAG缺陷型突变宿主细胞以及经酶处理去除GAGs的野生型细胞对寄生虫入侵具有一定的抵抗力。总之，这些研究表明硫酸化蛋白聚糖是刚地弓形虫用于识别底物和细胞的一个决定因素。这些受体的广泛分布可能有助于这种非常成功的细胞内寄生虫具有广泛的宿主和组织范围。
Toxoplasma gondii is an obligate intracellular parasite that actively invades a wide variety of vertebrate cells, although the basis of this pervasive cell recognition is not understood. We demonstrate here that binding to the substratum and to host cells is partially mediated by interaction with sulfated glycosaminoglycans (GAGs), Addition of excess soluble GAGs blocked parasite attachment to serum coated glass, thereby preventing gliding motility of extracellular parasites. Similarly, excess soluble GAGs decreased the attachment of parasites to human host cells from a variety of lineages, including monocytic, fibroblast, endothelial, epithelial, and macrophage cells. The inhibition of parasite attachment by GAGs was observed with heparin and heparan sulfate and also with chondroitin sulfates, indicating that the ligands for attachment are capable of recognizing a broad range of GAGs. The importance of sulfated proteoglycan recognition was further supported by the demonstration that GAG-deficient mutant host cells, and wild-type cells treated enzymatically to remove GAGs, were partially resistant to parasite invasion. Collectively, these studies reveal that sulfated proteoglycans are one determinant used for substrate and cell recognition by Toxoplasma, The widespread distribution of these receptors may contribute to the broad host and tissue ranges of this highly successful intracellular parasite.