Molecular Biology Institute, University of California, Los Angeles, CA 90095.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):17913-17923. doi: 10.1073/pnas.1909710117. Epub 2020 Jul 10.
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 and hookworm have highly dissimilar olfactory preferences, suggesting that these two species may use distinct strategies to target humans. CRISPR/Cas9-mediated mutagenesis of the 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.
全球约有 8 亿人感染了一种或多种穿透皮肤的线虫。这些寄生虫以发育停滞的第三期感染性幼虫（iL3）的形式在环境中持续存在，它们能够感知宿主发出的信号，接触宿主皮肤并穿透皮肤。然后，iL3 会在宿主内部重新启动发育，这一过程称为激活。在这里，我们研究了化学感觉如何驱动穿透皮肤的线虫寻找宿主和激活。我们发现，iL3 的嗅觉偏好与自由生活的成虫截然不同，这可能会限制 iL3 对宿主的寻找。人类寄生的毛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。利用 CRISPR/Cas9 介导的基因编辑技术，破坏了 iL3 对宿主散发的气味的吸引力，并阻止了激活。我们的研究结果表明，化学感觉在 iL3 寻找宿主和感染性方面起着重要作用，并为这些过程的分子机制提供了深入的了解。
