Host: Laura Duvall
Title: The neural basis of host seeking in skin-penetrating nematodes
Abstract: Skin-penetrating gastrointestinal parasitic nematodes infect over a billion people worldwide and are a major cause of neglected tropical disease. These parasites have an infective third-larval stage that actively searches for hosts to infect using host-emitted sensory cues. We are interested in understanding the host-seeking behaviors of infective larvae, as well as the molecular, cellular, and circuit mechanisms that underlie host seeking. We use the human-parasitic threadworm Strongyloides stercoralis for these studies because S. stercoralis is unique among parasitic nematodes in its amenability to genetic manipulation. We have shown that S. stercoralis infective larvae are robustly attracted to a diverse array of human-emitted odorants and mammalian body temperature. In this talk, I will focus primarily on our investigations into heat-seeking behavior. We found that CRISPR/Cas9-mediated targeted mutagenesis of the S. stercoralis homolog of the C. elegans cGMP-gated cation channel subunit gene tax-4 is required for heat seeking, indicating that conserved molecular pathways mediate thermotaxis in S. stercoralis and C. elegans. We then identified the primary thermosensory neurons in S. stercoralis, and found that they use a fundamentally different temperature-encoding strategy than the C. elegans thermosensory neurons. We further showed that S. stercoralis has three thermoreceptor proteins, one of which senses temperatures ranging from ambient to host body temperature and two of which are tuned specifically to temperatures near host body temperature. Thus, S. stercoralis sensory neurons show parasite-specific functional adaptations that support host seeking. Our results provide insight into the neural mechanisms that enable parasitic nematodes to find and infect humans.
Please email [email protected] for a link to the seminar.