Reactive Oxygen Species-mediated Immunity against Leishmania mexicana and Serratia marcescens in the Phlebotomine Sand Fly Lutzomyia longipalpis
Reactive Oxygen Species-mediated Immunity against Leishmania mexicana and Serratia marcescens in the Phlebotomine Sand Fly Lutzomyia longipalpis
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DOI：
10.1074/jbc.m112.376095
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发表时间：
2012-07-06
影响因子：
4.8
通讯作者：
Dillon, Rod J.
中科院分区：
文献类型：
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作者：
Diaz-Albiter, Hector;Sant'Anna, Mauricio R. V.;Dillon, Rod J.
白蛉是医学上重要的利什曼原虫病的媒介。利什曼原虫存在于白蛉肠道中，但对利什曼原虫存在的免疫反应的性质尚不清楚。活性氧是昆虫天然免疫途径中调节肠道微生物平衡的重要组成部分。在这里，我们表明，活性氧的浓度增加，在沙蝇中肠后，他们喂养的昆虫病原体粘质沙雷氏菌，但不喂养后，利什曼原虫，使用沙蝇作为载体。此外，利什曼原虫对ROS敏感，通过口服ROS给受感染的苍蝇或通过沉默表达白蛉ROS清除酶的基因。最后，用外源性ROS清除剂（尿酸）处理白蛉改变了肠道微生物的稳态，导致肠道微生物群增加，并降低了经口感染S. marcescens。我们的研究表明，白蛉ROS系统对肠道微生物群、昆虫病原体和利什曼原虫的不同反应，利什曼原虫利用白蛉作为哺乳动物宿主之间传播的媒介。
Phlebotomine sand flies are the vectors of medically important Leishmania. The Leishmania protozoa reside in the sand fly gut, but the nature of the immune response to the presence of Leishmania is unknown. Reactive oxygen species (ROS) are a major component of insect innate immune pathways regulating gut-microbe homeostasis. Here we show that the concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens but not after feeding on the Leishmania that uses the sand fly as a vector. Moreover, the Leishmania is sensitive to ROS either by oral administration of ROS to the infected fly or by silencing a gene that expresses a sand fly ROS-scavenging enzyme. Finally, the treatment of sand flies with an exogenous ROS scavenger (uric acid) altered the gut microbial homeostasis, led to an increased commensal gut microbiota, and reduced insect survival after oral infection with S. marcescens. Our study demonstrates a differential response of the sand fly ROS system to gut microbiota, an insect pathogen, and the Leishmania that utilize the sand fly as a vehicle for transmission between mammalian hosts.