Strongyloides species exhibit distinct behaviors on the skin of different mammals

Skin-penetrating nematodes, including the human parasite Strongyloides stercoralis and the rat parasite Strongyloides ratti, are gastrointestinal parasites that infect when infective third-stage larvae (iL3s) invade host skin. To enter the skin, iL3s engage in skin-penetration behavior, in which they repeatedly push and puncture the skin surface before ultimately burrowing into the skin. These parasites have narrow host ranges, but the extent to which skin-penetration behavior contributes to host specificity remains unclear. Here, we examine the behavior of S. stercoralis and S. ratti iL3s on skin from three different closely related rodents – rat, mouse, and gerbil – as well as the behavior of S. stercoralis iL3s on human skin to better understand how behavior differs on host vs. non-host skin. We used population and single-worm ex vivo skin-penetration assays to compare the behaviors of S. stercoralis and S. ratti iL3s on different skin types. We find that iL3s engage in repeated behavioral cycles on both host and non-host skin. However, these cycles vary across nematode species and skin types. S. ratti iL3s show similar behaviors on rat and mouse skin, although penetration takes longer to occur on mouse skin. In contrast, these iL3s show reduced and delayed skin-penetration behavior, and abort more skin-penetration attempts, on gerbil skin than on rat or mouse skin. S. stercoralis iL3s exhibit skin-penetration behavior at different frequencies on rat, mouse, gerbil, and human skin. These iL3s show increased skin-penetration behavior on gerbil skin relative to rat or mouse skin but show an even greater increase in behavior on human skin. Finally, we did not observe differences in iL3 behavior related to the age, sex, or genetic background of the host skin donor, suggesting that skin penetration is robust to differences in these host factors. Our results indicate that iL3s behave differently on different skin types and preferentially exhibit skin-penetration behavior on host skin or non-host skin from closely related mammals. Thus, enhanced skin-penetration behavior on host skin likely contributes to host selectivity.