Chemosensation in skin-penetrating parasitic nematodes

项目摘要 皮肤穿透线虫，包括人类寄生线虫Strongyloides stercoralis，几乎 世界上有10亿人，是低资源环境中发病率的主要来源。感染可引起 慢性胃肠道不适，儿童生长发育迟缓和认知障碍，甚至死亡 色葡萄粪感染S.粪蝇有一个复杂的生命周期，包括寄生一代内的 宿主和宿主之外自由生活的一代。在以前的工作中，我们发现碳的检测 二氧化碳（CO2）和宿主散发的气味对S.粪虫生活史此外，委员会认为， 我们发现，CO2和许多宿主散发的气味会引起特定生命阶段的行为反应， 感染性幼虫的化学感受偏好不同于非感染性生命阶段的化学感受偏好。 然而，介导这些化学感受反应的神经机制尚未被研究。 在这里，我们建议阐明化学感受的分子，细胞和电路机制， S.粪虫目的1：阐明S.粪虫 我们还将研究CO2微电路功能如何在生命阶段进行调制，以产生生命阶段- 对CO2的反应。在目标2中，我们将阐明介导对宿主反应的神经机制。 S.粪虫我们还将研究嗅觉微回路功能是如何通过 生命阶段在目标3中，我们将讨论化学感受的分子机制。我们将识别基因， 信号通路，介导响应CO2和主机发出的气味在S。粪虫我们还将 鉴定有助于寄生虫特异性和生命阶段特异性化学感受的分子机制 应答总之，我们的研究结果将提供关键的见解化学感受机制， 寄生线虫与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.