Filarial DAF-12 sense the host serum to resume iL3 development during infection.
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 Brugia malayi and Dirofilari...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011462 |
| _version_ | 1797786470680887296 |
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| author | Rémy Bétous Anthony Emile Hua Che Eva Guchen Didier Concordet Thavy Long Sandra Noack Paul M Selzer Roger Prichard Anne Lespine |
| author_facet | Rémy Bétous Anthony Emile Hua Che Eva Guchen Didier Concordet Thavy Long Sandra Noack Paul M Selzer Roger Prichard Anne Lespine |
| author_sort | Rémy Bétous |
| collection | DOAJ |
| description | 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 Brugia malayi and Dirofilaria immitis and compared them with DAF-12 from the non-filarial nematodes Haemonchus contortus and Caenorhabditis elegans. Interestingly, Dim and BmaDAF-12 exhibit high sequence identity and share a striking higher sensitivity than Hco and CelDAF-12 to the natural ligands Δ4- and Δ7-dafachronic acids (DA). Moreover, sera from different mammalian species activated specifically Dim and BmaDAF-12 while the hormone-depleted sera failed to activate the filarial DAF-12. Accordingly, hormone-depleted serum delayed the commencement of development of D. immitis iL3 in vitro. Consistent with these observations, we show that spiking mouse charcoal stripped-serum with Δ4-DA at the concentration measured in normal mouse serum restores its capacity to activate DimDAF-12. This indicates that DA present in mammalian serum participate in filarial DAF-12 activation. Finally, analysis of publicly available RNA sequencing data from B. malayi 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. |
| first_indexed | 2024-03-13T01:08:23Z |
| format | Article |
| id | doaj.art-0212e8c062b941028f67aae478da276b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-13T01:08:23Z |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0212e8c062b941028f67aae478da276b2023-07-06T05:30:56ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-06-01196e101146210.1371/journal.ppat.1011462Filarial DAF-12 sense the host serum to resume iL3 development during infection.Rémy BétousAnthony EmileHua CheEva GuchenDidier ConcordetThavy LongSandra NoackPaul M SelzerRoger PrichardAnne LespineNematode 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 Brugia malayi and Dirofilaria immitis and compared them with DAF-12 from the non-filarial nematodes Haemonchus contortus and Caenorhabditis elegans. Interestingly, Dim and BmaDAF-12 exhibit high sequence identity and share a striking higher sensitivity than Hco and CelDAF-12 to the natural ligands Δ4- and Δ7-dafachronic acids (DA). Moreover, sera from different mammalian species activated specifically Dim and BmaDAF-12 while the hormone-depleted sera failed to activate the filarial DAF-12. Accordingly, hormone-depleted serum delayed the commencement of development of D. immitis iL3 in vitro. Consistent with these observations, we show that spiking mouse charcoal stripped-serum with Δ4-DA at the concentration measured in normal mouse serum restores its capacity to activate DimDAF-12. This indicates that DA present in mammalian serum participate in filarial DAF-12 activation. Finally, analysis of publicly available RNA sequencing data from B. malayi 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.https://doi.org/10.1371/journal.ppat.1011462 |
| spellingShingle | Rémy Bétous Anthony Emile Hua Che Eva Guchen Didier Concordet Thavy Long Sandra Noack Paul M Selzer Roger Prichard Anne Lespine Filarial DAF-12 sense the host serum to resume iL3 development during infection. PLoS Pathogens |
| title | Filarial DAF-12 sense the host serum to resume iL3 development during infection. |
| title_full | Filarial DAF-12 sense the host serum to resume iL3 development during infection. |
| title_fullStr | Filarial DAF-12 sense the host serum to resume iL3 development during infection. |
| title_full_unstemmed | Filarial DAF-12 sense the host serum to resume iL3 development during infection. |
| title_short | Filarial DAF-12 sense the host serum to resume iL3 development during infection. |
| title_sort | filarial daf 12 sense the host serum to resume il3 development during infection |
| url | https://doi.org/10.1371/journal.ppat.1011462 |
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