Lymphatic filariasis (LF) afflicts over 60 million people worldwide and leads to severe pathological outcomes in chronic cases. The nematode parasites (Nematoda: Filarioidea) that cause LF require both arthropod (mosquito) intermediate hosts and mammalian definitive hosts for their propagation. The invasion and migration of filarial worms through host tissues are complex and critical to survival, yet little is known about the receptors and signaling pathways that mediate directed migration in these medically important species. In order to better understand the role of chemosensory signaling in filarial worm taxis, we employ comparative genomics, transcriptomics, reverse genetics, and chemical approaches to identify putative chemosensory receptor proteins and perturb chemotaxis phenotypes in filarial worms. We find that chemoreceptor family size is correlated with the presence of environmental (extrahost) stages in nematode life cycles, and that filarial worms contain compact and highly diverged chemoreceptor complements and lineage-specific ion channels that are predicted to operate downstream of chemoreceptor activation. In Brugia malayi, an etiological agent of LF, chemoreceptor expression patterns correspond to distinct parasite migration events across the life cycle. To interrogate the role of chemosensation in the migration of larval worms, arthropod and mammalian infectious stage Brugia parasites were incubated in nicotinamide, an agonist of the nematode transient receptor potential (TRP) channel OSM-9. Exposure of microfilariae to nicotinamide alters intramosquito migration, and exposure of L3s reduces chemotaxis toward host-associated cues in vitro. Nicotinamide also potently modulates thermosensory responses in L3s, suggesting a polymodal sensory role for Brugia osm-9. Reverse genetic studies implicate both Brugia osm-9 and the cyclic nucleotide–gated (CNG) channel subunit tax-4 in larval chemotaxis toward host serum, and these ion channel subunits partially rescue sensory defects in Caenorhabditis elegans osm-9 and tax-4 knock-out strains. Together, these data reveal genetic and functional diversification of chemosensory signaling proteins in filarial worms and encourage a more thorough investigation of clade- and parasite-specific facets of nematode sensory receptor biology.

淋巴丝虫病（LF）折磨着全世界超过6000万人，在慢性病例中导致严重的病理结果。导致LF的线虫寄生虫（线虫：Filarioidea）既需要节肢动物（蚊子）中间宿主，又需要哺乳动物定殖宿主才能繁殖。丝虫通过宿主组织的侵袭和迁移是复杂且对生存至关重要的，但对于介导这些医学上重要物种的定向迁移的受体和信号传导途径知之甚少。为了更好地理解化学感觉信号在丝虫滑行中的作用，我们采用比较基因组学，转录组学，反向遗传学和化学方法来鉴定丝虫中假定的化学感觉受体蛋白和扰动趋化性表型。我们发现化学感受器家族的大小与线虫生命周期中环境阶段（宿主外）的存在有关，丝虫中含有紧凑且高度分散的化学感受器补体和谱系特异性离子通道，这些离子通道预计将在化学感受器激活的下游起作用。在LF的病原体布鲁吉亚·马来（Brugia malayi），化学感受器的表达模式与整个生命周期中不同的寄生虫迁移事件相对应。为了询问化学传感在幼虫蠕虫迁移中的作用，将节肢动物和哺乳动物感染期的布鲁吉亚寄生虫在烟酰胺中孵育，该烟酰胺是线虫瞬时受体电位（TRP）通道OSM-9的激动剂。微丝虫暴露于烟酰胺会改变蚊内的迁移，而L3的暴露会降低体外对宿主相关线索的趋化性。烟酰胺还可以有效调节L3s中的热感觉反应，表明Brugia osm-9具有多峰感觉功能。反向遗传学研究表明布鲁加氏菌osm-9以及幼虫对宿主血清的趋化性中的环状核苷酸门控（CNG）通道亚基tax-4，这些离子通道亚基可部分挽救秀丽隐杆线虫osm-9和tax-4敲除菌株中的感觉缺陷。总之，这些数据揭示了丝虫中化学感觉信号蛋白的遗传和功能多样性，并鼓励对线虫感觉受体生物学的进化枝和寄生虫特异性方面进行更彻底的研究。