Neuronally sensed oxygen drives behavior and development in human-infective, skin-penetrating nematodes

Parasitic nematodes infect over a billion people worldwide and cause some of the most prevalent neglected tropical diseases ^1-5 . Many of these parasites are skin penetrating and have both extra-host life stages that inhabit host feces and surrounding soil, and intra-host life stages that inhabit host niches such as skin, vasculature, and intestine ^2,6-8 . Across life stages, these parasites encounter oxygen (O ₂ ) levels that range from ~21% at the soil-air interface to near-anaerobic levels in the host intestine ^9-12 . However, whether parasitic nematodes detect and respond to changes in O ₂ levels was unknown. Here, we examine O ₂ sensation in skin-penetrating parasitic nematodes and find that they show robust responses to changes in O ₂ levels. Moreover, their O ₂ -evoked behaviors differ from those of the free-living nematode Caenorhabditis elegans . We then investigate the molecular and neural mechanisms of O ₂ sensing in Strongyloides stercoralis , a genetically tractable human-infective nematode, and find that parasite-specific behavioral responses to O ₂ arise in part from evolutionary changes in their soluble guanylate cyclase repertoire. Finally, we find that neuronal O ₂ sensing regulates intra-host development in S. stercoralis . Our results demonstrate that skin-penetrating nematodes exhibit neuronally mediated O ₂ responses that are critical for multiple steps of their parasitic life cycle.