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Toxoplasma gondii Uses Sulfated Proteoglycans for Substrate and Host Cell Attachment

机译：弓形虫使用硫酸化蛋白聚糖进行底物和宿主细胞的附着

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摘要

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.
机译：弓形虫是一种专性的细胞内寄生虫，可主动侵入各种各样的脊椎动物细胞，尽管这种普遍的细胞识别的基础尚不清楚。我们在这里证明与基质和宿主细胞的结合是通过与硫酸化糖胺聚糖（GAGs）相互作用部分介导的。添加过量的可溶性GAG会阻止寄生虫附着在涂有血清的玻璃上，从而防止细胞外寄生虫滑行。同样，过量的可溶性GAG减少了寄生虫从多种谱系（包括单核细胞，成纤维细胞，内皮细胞，上皮细胞和巨噬细胞）到人宿主细胞的附着。用肝素和硫酸乙酰肝素以及硫酸软骨素观察到了GAG对寄生虫附着的抑制作用，表明附着的配体能够识别广泛的GAG。硫酸化蛋白聚糖识别的重要性进一步得到了证明，即GAG缺陷型突变宿主细胞和经过酶处理以去除GAG的野生型细胞对寄生虫入侵具有部分抵抗力。总的来说，这些研究表明硫酸化蛋白聚糖是弓形虫用于底物和细胞识别的决定因素。这些受体的广泛分布可能有助于这种高度成功的细胞内寄生虫的广泛宿主和组织范围。

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