The roles of two clip domain serine proteases in innate immune responses of the malaria vector Anopheles gambiae

The roles of two clip domain serine proteases in innate immune responses of the malaria vector Anopheles gambiae
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DOI:
10.1074/jbc.m506191200
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发表时间:
2005-12-02
影响因子:
4.8
通讯作者:
Müller, HM
Müller, HM
中科院分区:
生物学2区
文献类型:
--
作者:
Volz, J;Osta, MA;Müller, HM

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疟疾媒介冈比亚按蚊能够对疟原虫动合子产生多重免疫应答。在一些昆虫物种中积累的证据表明丝氨酸蛋白酶级联参与免疫应答的启动和协调。我们报告的分子和反向遗传特性的两个蚊子剪辑域丝氨酸蛋白酶,CLIPB14和CLIPB15,这两个蛋白酶参与在其他昆虫的酚氧化酶原激活的结构相似性。两种CLIP均在蚊子血细胞中表达,并由细菌和疟原虫攻击转录诱导。应用RNA干扰的功能研究表明,这两个CLIP参与杀灭按蚊体内的疟原虫动卵细胞。对寄生虫黑化的研究证明了CLIPB14在酚氧化酶原级联中的额外作用。我们进一步报告,这两个CLIP参与防御革兰氏阴性菌。我们的研究结果有力地表明,剪辑结构域丝氨酸蛋白酶提供多种功能,并发挥独特的作用,在几个免疫途径的A。冈比亚。
The malaria vector Anopheles gambiae is capable of multiple immune responses against Plasmodium ookinetes. Accumulating evidence in several insect species suggests the involvement of serine protease cascades in the initiation and coordination of immune responses. We report molecular and reverse genetic characterization of two mosquito clip domain serine proteases, CLIPB14 and CLIPB15, which share structural similarity to proteases involved in prophenoloxidase activation in other insects. Both CLIPs are expressed in mosquito hemocytes and are transcriptionally induced by bacterial and Plasmodium challenges. Functional studies applying RNA interference revealed that both CLIPs are involved in the killing of Plasmodium ookinetes in Anopheles. Studies on parasite melanization demonstrated an additional role for CLIPB14 in the prophenoloxidase cascade. We further report that both CLIPs participate in defense toward Gram-negative bacteria. Our findings strongly suggest that clip domain serine proteases serve multiple functions and play distinctive roles in several immune pathways of A. gambiae.