A role for heparan sulfate proteoglycans in Plasmodium falciparum sporozoite invasion of anopheline mosquito salivary glands.

A role for heparan sulfate proteoglycans in Plasmodium falciparum sporozoite invasion of anopheline mosquito salivary glands.
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DOI:
10.1042/bj20110694
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发表时间:
2011-09-15
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
Dinglasan RR
Dinglasan RR
中科院分区:
其他
文献类型:
--
作者:
Armistead JS;Wilson IB;van Kuppevelt TH;Dinglasan RR

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硫酸乙酰肝素(HS)已被证明是疟原虫子孢子归巢和侵入肝脏的重要介质,但这种糖胺聚糖在蚊子载体宿主-子孢子相互作用中的作用尚不清楚。我们已经生化特性的AgOXT 1(冈比亚按蚊肽-O-木糖基转移酶1)的功能,并证实,AgOXT 1可以修改代表模型HS和硫酸软骨素蛋白聚糖在体外的肽。此外,我们还证明了蚊子唾液腺基底膜蛋白聚糖被HS修饰。我们使用RNA干扰介导的敲低A. gambiae唾液腺,以确定从蚊子中肠卵囊释放的恶性疟原虫子孢子是否使用唾液腺HS作为组织侵入的受体。我们的研究结果表明,唾液腺基膜HS糖胺聚糖只部分介导中肠子孢子入侵该组织,在没有HS的情况下,其他表面共受体的存在足以促进寄生虫进入。
HS (heparan sulfate) has been shown to be an important mediator of Plasmodium sporozoite homing and invasion of the liver, but the role of this glycosaminoglycan in mosquito vector host–sporozoite interactions is unknown. We have biochemically characterized the function of AgOXT1 (Anopheles gambiae peptide-O-xylosyltransferase 1) and confirmed that AgOXT1 can modify peptides representing model HS and chondroitin sulfate proteoglycans in vitro. Moreover, we also demonstrated that the mosquito salivary gland basal lamina proteoglycans are modified by HS. We used RNA interference-mediated knockdown of HS biosynthesis in A. gambiae salivary glands to determine whether Plasmodium falciparum sporozoites that are released from mosquito midgut oocysts use salivary gland HS as a receptor for tissue invasion. Our results suggest that salivary gland basal lamina HS glycosaminoglycans only partially mediate midgut sporozoite invasion of this tissue, and that in the absence of HS, the presence of other surface co-receptors is sufficient to facilitate parasite entry.