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

<p>The <i>S</i>. <i>stercoralis</i> 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 <i>Ss</i>-DAF-12, with liganded <i>Ss</i>-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 <i>Ss</i>-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 <i>Ss</i>-DAF-12, stimulated by increased biosynthesis of its steroid ligand.