Mangelsdorf, David J.

Significance The intestinal parasite Strongyloides stercoralis infects an estimated 100 million people. This nematode’s unique ability to autoinfect its host enables it to persist for decades undetected and to progress to a potentially fatal hyperinfection that often is induced by glucocorticoid treatment. We report a mouse model, involving the NSG strain, that recapitulates all forms of human strongyloidiasis. Even in severely immunocompromised NSG mice, glucocorticoid treatment was required for autoinfection, raising intriguing questions about the mechanism of glucocorticoid action. Notably, administering a nematode-derived steroid, Δ7-dafachronic acid, which acts through a receptor within S. stercoralis to regulate parasite development, significantly diminished autoinfection in glucocorticoid-treated NSG mice. This opens the possibility of new chemotherapy for hyperinfective strongyloidiasis, targeting the parasite’s own steroid hormone mechanisms.