{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:48:59Z","timestamp":1792154939553,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011462","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022077","name":"INRAE","doi-asserted-by":"crossref","award":["newly recruited researchers grant"],"award-info":[{"award-number":["newly recruited researchers grant"]}],"id":[{"id":"10.13039\/501100022077","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2017-04010"],"award-info":[{"award-number":["RGPIN-2017-04010"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Nematode parasites enter their definitive host at the developmentally arrested infectious larval stage (iL3), and the ligand-dependent nuclear receptor DAF-12 contributes to trigger their development to adulthood. Here, we characterized DAF-12 from the filarial nematodes <jats:italic>Brugia malayi<\/jats:italic> and <jats:italic>Dirofilaria immitis<\/jats:italic> and compared them with DAF-12 from the non-filarial nematodes <jats:italic>Haemonchus contortus<\/jats:italic> and <jats:italic>Caenorhabditis elegans<\/jats:italic>. Interestingly, <jats:italic>Dim<\/jats:italic> and <jats:italic>Bma<\/jats:italic>DAF-12 exhibit high sequence identity and share a striking higher sensitivity than <jats:italic>Hco<\/jats:italic> and <jats:italic>Cel<\/jats:italic>DAF-12 to the natural ligands \u03944- and \u03947-dafachronic acids (DA). Moreover, sera from different mammalian species activated specifically <jats:italic>Dim<\/jats:italic> and <jats:italic>Bma<\/jats:italic>DAF-12 while the hormone-depleted sera failed to activate the filarial DAF-12. Accordingly, hormone-depleted serum delayed the commencement of development of <jats:italic>D<\/jats:italic>. <jats:italic>immitis iL3 in vitro<\/jats:italic>. Consistent with these observations, we show that spiking mouse charcoal stripped-serum with \u03944-DA at the concentration measured in normal mouse serum restores its capacity to activate <jats:italic>Dim<\/jats:italic>DAF-12. This indicates that DA present in mammalian serum participate in filarial DAF-12 activation. Finally, analysis of publicly available RNA sequencing data from <jats:italic>B<\/jats:italic>. <jats:italic>malayi<\/jats:italic> showed that, at the time of infection, putative gene homologs of the DA synthesis pathways are coincidently downregulated. Altogether, our data suggest that filarial DAF-12 have evolved to specifically sense and survive in a host environment, which provides favorable conditions to quickly resume larval development. This work sheds new light on the regulation of filarial nematodes development while entering their definitive mammalian host and may open the route to novel therapies to treat filarial infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011462","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T17:27:50Z","timestamp":1687282070000},"page":"e1011462","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Filarial DAF-12 sense the host serum to resume iL3 development during 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