Chemosensory mechanisms of host seeking and infectivity in skin-penetrating nematodes
Chemosensory mechanisms of host seeking and infectivity in skin-penetrating nematodes
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DOI：
10.1073/pnas.1909710117
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发表时间：
2020-07-28
影响因子：
11.1
通讯作者：
Hallem, Elissa A.
中科院分区：
文献类型：
--
作者：
Gang, Spencer S.;Castelletto, Michelle L.;Hallem, Elissa A.
全世界约有8亿人感染了一种或多种皮肤穿透性线虫。这些寄生虫作为发育受阻的第三阶段感染幼虫（il - 3）在环境中持续存在，它们向宿主发出的信号导航，接触宿主皮肤，并穿透皮肤。然后，il - 3会根据感觉信号在宿主体内重新启动发育，这一过程被称为激活。在这里，我们研究了化学感觉如何驱动皮肤穿透线虫的寄主寻找和激活。我们发现，il - 3的嗅觉偏好与自由生活的成年人截然不同，这可能限制了宿主对il - 3的寻找。人类寄生的粪圆线虫和钩虫具有高度不同的嗅觉偏好，这表明这两个物种可能使用不同的策略来针对人类。CRISPR/ cas9介导的S. stercoralis tax-4基因突变消除了il - 3对宿主发出气味的吸引力，并阻止了其活化。我们的研究结果表明，化学感觉在il - 3寻找宿主和感染性中起着重要作用，并为这些过程背后的分子机制提供了见解。
Approximately 800 million people worldwide are infected with one or more species of skin-penetrating nematodes. These parasites persist in the environment as developmentally arrested third-stage infective larvae (iL3s) that navigate toward host-emitted cues, contact host skin, and penetrate the skin. iL3s then reinitiate development inside the host in response to sensory cues, a process called activation. Here, we investigate how chemosensation drives host seeking and activation in skin-penetrating nematodes. We show that the olfactory preferences of iL3s are categorically different from those of free-living adults, which may restrict host seeking to iL3s. The human-parasitic threadworm Strongyloides stercoralis and hookworm Ancylostoma ceylanicum have highly dissimilar olfactory preferences, suggesting that these two species may use distinct strategies to target humans. CRISPR/Cas9-mediated mutagenesis of the S. stercoralis tax-4 gene abolishes iL3 attraction to a host-emitted odorant and prevents activation. Our results suggest an important role for chemosensation in iL3 host seeking and infectivity and provide insight into the molecular mechanisms that underlie these processes.