Chemosensation in skin-penetrating parasitic nematodes

项目总结 穿透皮肤的线虫，包括人类寄生的粗线虫，感染几乎 全球有10亿人口，在资源匮乏的情况下，它是发病率的主要来源。感染可能会导致 儿童慢性胃肠道不适、发育迟缓和认知障碍，甚至死亡 病原菌的感染。有一个复杂的生活史，其中包括寄生世代在 寄主和在寄主之外自由生活的一代。在之前的工作中，我们证明了碳的检测 二氧化碳(CO2)和寄主散发的气味对斯特氏假单胞菌生活史的多个阶段很重要。此外， 我们发现，二氧化碳和许多宿主排放的气味会引发特定于生命阶段的行为反应，从而 感染幼虫的化学感觉偏好与非感染幼虫的不同。 然而，介导这些化学感觉反应的神经机制尚未被研究。 在这里，我们建议阐明化学感觉的分子、细胞和电路机制。 Steccoralis.在目标1中，我们将阐明在粪藻中介导二氧化碳反应的神经机制。 我们还将研究二氧化碳微电路功能是如何在生命阶段调节的，以产生生命阶段-- 对二氧化碳的特定反应。在目标2中，我们将阐明介导对宿主的反应的神经机制- 在紫珊瑚中散发出的气味。我们还将研究嗅觉微电路功能是如何在 生命的各个阶段。在目标3中，我们将讨论化学感觉的分子机制。我们将确定基因和 介导对二氧化碳和寄主散发的气味的反应的信号通路。我们还将 确定促进寄生虫特异性和生活期特异性化学感觉的分子机制 回应。综上所述，我们的结果将为化学传感机制提供关键的见解。 寄生线虫与其人类宿主的复杂相互作用。

PROJECT SUMMARY Skin-penetrating nematodes, including the human-parasitic threadworm Strongyloides stercoralis, infect nearly one billion people worldwide and are a major source of morbidity in low-resource settings. Infections can cause chronic gastrointestinal distress, stunted growth and cognitive impairment in children, and even death in the case of S. stercoralis infection. S. stercoralis has a complex life cycle that includes a parasitic generation inside the host and a free-living generation outside the host. In previous work, we showed that the detection of carbon dioxide (CO2) and host-emitted odorants is important for multiple stages of the S. stercoralis life cycle. Moreover, we showed that CO2 and many host-emitted odorants elicit life-stage-specific behavioral responses, such that the chemosensory preferences of the infective larvae are distinct from those of the non-infective life stages. However, the neural mechanisms that mediate these chemosensory responses have not yet been investigated. Here, we propose to elucidate the molecular, cellular, and circuit mechanisms of chemosensation in S. stercoralis. In Aim 1, we will elucidate the neural mechanisms that mediate CO2 response in S. stercoralis. We will also investigate how CO2 microcircuit function is modulated across life stages to generate life-stage- specific responses to CO2. In Aim 2, we will elucidate the neural mechanisms that mediate responses to host- emitted odorants in S. stercoralis. We will also investigate how olfactory microcircuit function is modulated across life stages. In Aim 3, we will address the molecular mechanisms of chemosensation. We will identify genes and signaling pathways that mediate responses to CO2 and host-emitted odorants in S. stercoralis. We will also identify molecular mechanisms that contribute to parasite-specific and life-stage-specific chemosensory responses. Taken together, our results will provide key insights into the chemosensory mechanisms that underlie the complex interactions of parasitic nematodes with their human hosts.