An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites
An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites
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DOI：
10.1073/pnas.0508335102
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发表时间：
2005-11-08
影响因子：
11.1
通讯作者：
Michel, K
中科院分区：
文献类型：
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作者：
Abraham, EG;Pinto, SB;Michel, K
我们使用系统发育、分子、反向遗传和细胞生物学工具对斯氏按蚊和冈比亚按蚊同源SRPN6基因进行了功能分析。这些结果强烈暗示SRPN6参与了针对疟原虫的先天免疫反应。该基因属于一个蚊子特有的基因簇，其中包括另外三个蛇按蚊。SRPN6可被大肠杆菌、啮齿动物和人疟原虫诱导表达。该基因特异性表达于被眼动疟原虫侵袭的中肠细胞以及循环和附着的血细胞中。RNA干扰对易感An中SRPN6表达的抑制作用。斯蒂芬氏菌导致寄生虫数量大幅增加，而在易感的安。冈比亚延缓了寄生虫裂解的进程，而不影响发育中的寄生虫的数量。然而，安。gbiae SRPN6敲低会增加L3-5难降解菌株和缺乏CTL4的G3易感蚊子中黑化寄生虫的数量。这些结果表明，AsSRPN6参与了寄生虫的杀伤过程，而AgSRPN6通过抑制黑色素化和/或促进寄生虫裂解来清除寄生虫。我们认为，这些观察到的表型差异是由于两种蚊子各自的目标丝氨酸蛋白酶的作用发生了变化。
We have functionally analyzed the orthologous SRPN6 genes from Anopheles stephensi and Anopheles gambiae using phylogenetic, molecular, reverse genetic, and cell biological tools. The results strongly implicate SRPN6 in the innate immune response against Plasmodium. This gene belongs to a mosquito-specific gene cluster including three additional Anopheles serpins. SRPN6 expression is induced by Escherichia coli and both rodent and human malaria parasites. The gene is specifically expressed in midgut cells invaded by Plasmodium ookinetes and in circulating and attached hemocytes. Knockdown of SRPN6 expression by RNA interference in susceptible An. stephensi leads to substantially increased parasite numbers, whereas depletion in susceptible An. gambiae delays progression of parasite lysis without affecting the number of developing parasites. However, the An. gambiae SRPN6 knockdown increases the number of melanized parasites in the L3-5 refractory strain and in susceptible G3 mosquitoes depleted of CTL4. These results indicate that AsSRPN6 is involved in the parasite-killing process, whereas AgSRPN6 acts on parasite clearance by inhibiting melanization and/or promoting parasite lysis. We propose that these observed phenotypic differences are due to changed roles of the respective target serine proteases in the two mosquito species.