The neural basis of temperature-driven host seeking in the human threadworm Strongyloides stercoralis

Soil-transmitted parasitic nematodes infect approximately one billion people and are a major cause of morbidity worldwide1-8. The infective larvae (iL3s) of these parasites actively search for hosts in a poorly understood, sensory-driven process that requires thermal cues9,10. Here, we describe the neural basis of temperature-driven host seeking in parasitic nematodes using the human threadworm Strongyloides stercoralis. We show that S. stercoralis thermosensation is mediated by the AFD neurons, a thermosensory neuron class that is conserved between parasitic and free-living nematodes11. We demonstrate that S. stercoralis AFD displays parasite-specific adaptations that enable both nonlinear and linear encoding of temperatures up to human body temperature. Furthermore, we describe a novel thermosensory behavior in which S. stercoralis iL3s generate spontaneous reversals of temperature preference at below-body temperatures. Finally, we identify three thermoreceptors selectively expressed in S. stercoralis AFD that display parasite-specific sensitivities to human body temperatures and likely enable temperature-driven host seeking by iL3s. Our results are the first direct evidence that the sensory neurons of soil-transmitted parasitic nematodes exhibit parasite-specific neural adaptations and sensory coding strategies that allow them to target human hosts, a finding with important implications for efforts to develop new therapeutic strategies for nematode control.