Skin-penetration behaviors of the human-infective worm Strongyloides stercoralis
Elissa A. Hallem, Ph.D.
Department of Microbiology, Immunology, and Molecular Genetics
University of California, Los Angeles
We study the neural basis of parasitic behaviors using the skin-penetrating nematode Strongyloides stercoralis, a gastrointestinal parasite that infects over 600 million people worldwide. S. stercoralis infective larvae invade human hosts by penetrating through skin, but the behaviors and underlying mechanisms that drive skin penetration are poorly understood. We are investigating skin penetration at the level of genes, neurons, and behavior. We first designed an ex vivo assay that enabled us to visualize the behavior of infective larvae on either rat or human skin. We then used this assay to show that infective larvae engage in repeated cycles of pushing, puncturing, and crawling on the skin surface before ultimately penetrating into the skin. S. stercoralis infective larvae push against human skin more frequently than rat skin, consistent with an increased drive to penetrate host skin. Moreover, exposure to human foot odor and human-associated odorants enhances penetration by S. stercoralis but not the closely related rat parasite Strongyloides ratti, suggesting that chemosensation contributes to the ability of infective larvae to distinguish host from non-host skin. We then investigated the neural mechanisms underlying skin penetration. We found that CRISPR-mediated disruption of dopamine biosynthesis, chemogenetic silencing of dopaminergic neurons, and CRISPR-mediated disruption of a nematode-specific mechanoreceptor gene expressed in the dopaminergic neurons severely inhibits skin penetration. Our results demonstrate that dopamine signaling plays an essential role in driving skin penetration and raise the possibility that compounds that block nematode-specific components of the dopaminergic pathway could be developed into topical repellents.