PDF(Pubmed)
Abstract：
Skin-penetrating nematodes infect nearly one billion people worldwide. The developmentally arrested infective larvae (iL3s) seek out hosts, invade hosts via skin penetration, and resume development inside the host in a process called activation. Activated infective larvae (iL3as) traverse the host body, ending up as parasitic adults in the small intestine. Skin-penetrating nematodes respond to many chemosensory cues, but how chemosensation contributes to host seeking, intra-host development, and intra-host navigation - three crucial steps of the parasite-host interaction - remains poorly understood. Here, we investigate the role of carbon dioxide (CO2) in promoting parasite-host interactions in the human-infective threadworm Strongyloides stercoralis. We show that S. stercoralis exhibits life-stage-specific preferences for CO2: iL3s are repelled, non-infective larvae and adults are neutral, and iL3as are attracted. CO2 repulsion in iL3s may prime them for host seeking by stimulating dispersal from host feces, while CO2 attraction in iL3as may direct worms toward high-CO2 areas of the body such as the lungs and intestine. We also identify sensory neurons that detect CO2; these neurons are depolarized by CO2 in iL3s and iL3as. In addition, we demonstrate that the receptor guanylate cyclase Ss-GCY-9 is expressed specifically in CO2-sensing neurons and is required for CO2-evoked behavior. Ss-GCY-9 also promotes activation, indicating that a single receptor can mediate both behavioral and physiological responses to CO2. Our results illuminate chemosensory mechanisms that shape the interaction between parasitic nematodes and their human hosts and may aid in the design of novel anthelmintics that target the CO2-sensing pathway.
摘要：
皮肤穿透性线虫感染全球近10亿人。发育停滞的感染性幼虫（iL3s）寻找宿主，通过皮肤渗透侵入宿主，并在称为激活的过程中恢复主机内部的开发。激活的感染性幼虫（iL3as）穿过宿主身体，最终成为小肠中的寄生虫。穿透皮肤的线虫对许多化学感应线索有反应，但是化学感觉如何有助于寻找宿主，宿主内开发，和宿主内导航-寄生虫-宿主相互作用的三个关键步骤-仍然知之甚少。这里,我们研究了二氧化碳（CO2）在促进人类感染的线虫中寄生虫-宿主相互作用中的作用。我们证明了S.stercoralis对CO2表现出生命阶段特定的偏好：iL3被排斥，非感染性幼虫和成虫是中性的，iL3as被吸引了。iL3s中的CO2排斥可能会通过刺激宿主粪便的扩散来引发宿主寻找，而iL3as中的CO2吸引力可能会将蠕虫引向身体的高CO2区域，如肺部和肠道。我们还鉴定了检测CO2的感觉神经元；这些神经元在iL3s和iL3as中被CO2去极化。此外,我们证明了受体鸟苷酸环化酶Ss-GCY-9在CO2感应神经元中特异性表达，并且是CO2诱发行为所必需的。Ss-GCY-9也促进激活，表明单个受体可以介导对CO2的行为和生理反应。我们的结果阐明了化学感应机制，这些机制塑造了寄生线虫与其人类宿主之间的相互作用，并可能有助于设计针对CO2传感途径的新型驱虫药。
