Hypothesized regulation of the Strongyloides stercoralis life cycle by the nuclear hormone receptor DAF-12.

The S. stercoralis parasitic female (P Female) produces larval progeny by mitotic parthenogenesis, and these progeny have several possible developmental fates. A female post-parasitic first-stage larva (PP L1) can either precociously develop inside the host to an autoinfective third-stage larva (L3a), which develops to a second-generation parasitic female, or be passed in the feces to develop outside the host by one of two routes: a homogonic route directly to a developmentally arrested infectious third-stage larva (iL3), which is favored at host-like temperatures (e.g., 37°C), or a heterogonic route to a free-living adult female (FL Female), which is favored at lower temperatures (e.g., 22°C). We hypothesize that this developmental checkpoint is regulated by dafachronic acid ligands for the nuclear hormone receptor Ss-DAF-12, with liganded Ss-DAF-12 favoring heterogonic development. Larval progeny of the single free-living generation of females and males invariably form iL3, and this developmental arrest is hypothesized to be governed by the absence of Ss-DAF-12 signaling. Once inside a host, the third-stage larva resumes development and feeding, resulting in a form designated the L3+. We hypothesize that resumption of development by iL3 entering the host and maturation to the P Female requires an increase in signaling by Ss-DAF-12, stimulated by increased biosynthesis of its steroid ligand.