Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Curr Biol. 2022 May 23;32(10):2206-2221.e6. doi: 10.1016/j.cub.2022.04.010. Epub 2022 Apr 27.
Soil-transmitted parasitic nematodes infect over one billion people and cause devastating morbidity worldwide. Many of these parasites have infective larvae that locate hosts using thermal cues. Here, we identify the thermosensory neurons of the human threadworm Strongyloides stercoralis and show that they display unique functional adaptations that enable the precise encoding of temperatures up to human body temperature. We demonstrate that experience-dependent thermal plasticity regulates the dynamic range of these neurons while preserving their ability to encode host-relevant temperatures. We describe a novel behavior in which infective larvae spontaneously reverse attraction to heat sources at sub-body temperatures and show that this behavior is mediated by rapid adaptation of the thermosensory neurons. Finally, we identify thermoreceptors that confer parasite-specific sensitivity to body heat. Our results pinpoint the parasite-specific neural adaptations that enable parasitic nematodes to target humans and provide the foundation for drug development to prevent human infection.
土壤传播的寄生线虫感染了超过 10 亿人，并在全球范围内造成严重的发病率。这些寄生虫中有许多具有感染性幼虫，它们利用热线索来定位宿主。在这里，我们确定了人类粪类圆线虫的热敏神经元，并表明它们具有独特的功能适应性，能够精确编码高达人体温度的温度。我们证明，经验依赖性热塑性调节这些神经元的动态范围，同时保持它们编码宿主相关温度的能力。我们描述了一种新的行为，即感染性幼虫在体温以下会自发地逆转对热源的吸引力，并且表明这种行为是由热敏神经元的快速适应介导的。最后，我们确定了赋予寄生虫对体热特异性敏感性的热感受器。我们的研究结果指出了使寄生线虫能够针对人类的寄生虫特异性神经适应，并为预防人类感染的药物开发提供了基础。
