Plasmodium ookinete-secreted proteins secreted through a common micronemal pathway are targets of blocking malaria transmission
Plasmodium ookinete-secreted proteins secreted through a common micronemal pathway are targets of blocking malaria transmission
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DOI：
10.1074/jbc.m401385200
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发表时间：
2004-06-18
影响因子：
4.8
通讯作者：
Vinetz, JM
中科院分区：
文献类型：
--
作者：
Li, FW;Templeton, TJ;Vinetz, JM
疟疾寄生虫疟原虫的蚊子中肠动合子阶段具有微丝分泌细胞器，其介导运动和中肠壁出口以建立孢子生殖阶段和随后的传播。本研究的目的有两个：1）确定是否存在一个单一的微线群体的可溶性和膜相关分泌蛋白;（2）对动合子微丝蛋白几丁质酶（PgCHT 1）、环子孢子和TRAP相关蛋白（CTRP）进行鉴定，和血管性血友病因子A结构域相关蛋白（WARP）作为免疫学靶点引发对蚊子的血清阻断疟疾寄生虫感染性。间接免疫荧光定位研究表明，在疟原虫gallinaceum使用特异性抗血清，所有三种蛋白质分布在细胞内具有类似的颗粒状细胞质外观和焦点浓度的PgCHT 1和PgCTRP，但不是PgWARP，在动合子顶端。免疫金双标记电子显微镜，使用抗血清对膜相关蛋白CTRP和可溶性WARP，表明这两种蛋白质共定位于相同的微线人口。在微线内，CTRP在微线膜处与外周相关，而PgCHT 1和WARP在微线腔内弥漫。抗恶性疟原虫WARP血清显著降低了鸡疟原虫对埃及伊蚊和恶性疟原虫对按蚊的感染性。抗PgCTRP和PgCHT 1的抗血清也显著降低了鸡疫霉对A.埃及人。这些结果支持的概念，动合子微线蛋白可能构成一个一般类的疟疾传播阻断疫苗候选人。
The mosquito midgut ookinete stage of the malaria parasite, Plasmodium, possesses microneme secretory organelles that mediate locomotion and midgut wall egress to establish sporogonic stages and subsequent transmission. The purpose of this study was 2-fold: 1) to determine whether there exists a single micronemal population with respect to soluble and membrane-associated secreted proteins; and 2) to evaluate the ookinete micronemal proteins chitinase (PgCHT1), circumsporozoite and TRAP-related protein (CTRP), and von Willebrand factor A domain-related protein ( WARP) as immunological targets eliciting sera-blocking malaria parasite infectivity to mosquitoes. Indirect immunofluorescence localization studies in Plasmodium gallinaceum using specific antisera showed that all three proteins are distributed intracellularly with a similar granular cytoplasmic appearance and with focal concentration of PgCHT1 and PgCTRP, but not PgWARP, at the ookinete apical end. Immunogold double-labeling electron microscopy, using antisera against the membrane-associated protein CTRP and the soluble WARP, showed that these two proteins co-localized to the same micronemal population. Within the microneme CTRP was associated peripherally at the microneme membrane, whereas PgCHT1 and WARP were diffuse within the micronemal lumen. Sera produced against Plasmodium falciparum WARP significantly reduced the infectivity of P. gallinaceum to Aedes aegypti and P. falciparum to Anopheles mosquitoes. Antisera against PgCTRP and PgCHT1 also significantly reduced the infectivity of P. gallinaceum for A. aegypti. These results support the concept that ookinete micronemal proteins may constitute a general class of malaria transmission-blocking vaccine candidates.