Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.
Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae.
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DOI：
10.1038/srep27838
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发表时间：
2016-06-09
影响因子：
4.6
通讯作者：
Yang CW
中科院分区：
文献类型：
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作者：
Chang MY;Cheng YC;Hsu SH;Ma TL;Chou LF;Hsu HH;Tian YC;Chen YC;Sun YJ;Hung CC;Pan RL;Yang CW
钩端螺旋体病是一种经常被忽视的急性肾损伤的原因，可导致多器官衰竭，甚至死亡。在许多致病性钩端螺旋体中保守的主要蛋白是外膜蛋白LipL 32。然而，LipL 32在钩端螺旋体病肾损伤发病机制中的作用尚不完全清楚。本文研究了LipL 32对斑马鱼幼鱼肾脏发育的影响。斑马鱼幼鱼与桑塔罗塞钩端螺旋体血清型Shermani孵育引起急性肾小管损伤，主要是在近端前肾管。此外，显微注射lipl 32 mRNA或重组LipL 32蛋白到斑马鱼幼虫中增加巨噬细胞的积累，并破坏NA-K-ATP酶在前肾管中的基底外侧位置。这些变化导致原肾结构严重受损。我们进一步证明，吗啉敲低tlr 2，但不是tlr 4，减少LipL 32诱导的白细胞浸润和肾损伤。这些数据表明，LipL 32有助于钩端螺旋体病的肾脏病理学，并提供了一些线索，LipL 32的潜在毒力。我们的研究结果支持使用斑马鱼作为模式生物研究钩端螺旋体感染的疾病机制。这种模型可能允许未来的探索不同的钩端螺旋体外膜蛋白的毒力和分子途径。
Leptospirosis is an often overlooked cause of acute kidney injury that can lead to multiple organ failure and even death. The principle protein that conserved in many pathogenic leptospires is the outer membrane protein LipL32. However, the role of LipL32 in the pathogenesis of renal injury in leptospirosis is not entirely clear. Here we studied the effects of LipL32 on the developing kidney in zebrafish larvae. Incubation of zebrafish larvae with Leptospira santarosai serovar Shermani induced acute tubular injury predominantly in the proximal pronephric ducts. Furthermore, microinjection of lipl32 mRNA or recombinant LipL32 protein into zebrafish larvae increased macrophage accumulation and disrupted the basolateral location of NA-K-ATPase in pronephric ducts. These changes led to substantial impairment of the pronephric kidney structure. We further demonstrated that morpholino knockdown of tlr2, but not tlr4, reduced the LipL32-induced leukocyte infiltration and kidney injury. These data demonstrate that LipL32 contributes to the renal pathology in leptospirosis and gives some clues to the potential virulence of LipL32. Our results support the use of zebrafish as a model organism for studying the disease mechanism of leptospiral infection. This model might permit the future exploration of the virulence and molecular pathways of different leptospiral outer membrane proteins.