Instituto Oswaldo Cruz, Fiocruz, Av. Brasil 4365, 21045-900, Rio de Janeiro, Brazil.
J Biol Chem. 2012 Apr 13;287(16):12985-93. doi: 10.1074/jbc.M111.331561. Epub 2012 Feb 28.
Female phlebotomine sand flies Lutzomyia longipalpis naturally harbor populations of the medically important Leishmania infantum (syn. Leishmania chagasi) parasite in the gut, but the extent to which the parasite interacts with the immune system of the insect vector is unknown. To investigate the sand fly immune response and its interaction with the Leishmania parasite, we identified a homologue for caspar, a negative regulator of immune deficiency signaling pathway. We found that feeding antibiotics to adult female L. longipalpis resulted in an up-regulation of caspar expression relative to controls. caspar was differentially expressed when females were fed on gram-negative and gram-positive bacterial species. caspar expression was significantly down-regulated in females between 3 and 6 days after a blood feed containing Leishmania mexicana amastigotes. RNA interference was used to deplete caspar expression in female L. longipalpis, which were subsequently fed with Leishmania in a blood meal. Sand fly gut populations of both L. mexicana and L. infantum were significantly reduced in caspar-depleted females. The prevalence of L. infantum infection in the females fell from 85 to 45%. Our results provide the first insight into the operation of immune homeostasis in phlebotomine sand flies during the growth of bacterial and Leishmania populations in the digestive tract. We have demonstrated that the activation of the sand fly immune system, via depletion of a single gene, can lead to the abortion of Leishmania development and the disruption of transmission by the phlebotomine sand fly.
雌性白蛉沙蝇（Lutzomyia longipalpis）在肠道中自然携带医学上重要的利什曼原虫（即利什曼原虫 chagasi）寄生虫，但寄生虫与昆虫媒介的免疫系统相互作用的程度尚不清楚。为了研究沙蝇的免疫反应及其与利什曼原虫寄生虫的相互作用，我们鉴定了 caspar 的同源物，caspar 是免疫缺陷信号通路的负调控因子。我们发现，给成年雌性白蛉沙蝇喂食抗生素会导致 caspar 表达相对于对照上调。当雌性沙蝇以革兰氏阴性和革兰氏阳性细菌物种为食时，caspar 的表达存在差异。当雌性沙蝇在含有利什曼原虫无鞭毛体的血液中进食 3 至 6 天后，caspar 的表达显著下调。使用 RNA 干扰耗尽雌性白蛉沙蝇中的 caspar 表达，随后在血液餐中用利什曼原虫喂养。在 caspar 耗尽的雌性沙蝇中，利什曼原虫和利什曼原虫肠道种群的数量明显减少。caspar 耗尽的雌性沙蝇中利什曼原虫感染的流行率从 85%降至 45%。我们的研究结果首次揭示了在肠道中细菌和利什曼原虫种群生长过程中，白蛉沙蝇的免疫稳态的运作情况。我们已经证明，通过耗尽单个基因来激活沙蝇的免疫系统，可以导致利什曼原虫的发育中断，并破坏白蛉沙蝇的传播。
