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In the model host caenorhabditis elegans, sphingosine-1-phosphate-mediated signaling increases immunity toward human opportunistic bacteria
- Title
- In the model host caenorhabditis elegans, sphingosine-1-phosphate-mediated signaling increases immunity toward human opportunistic bacteria
- Authors
- Lee K.; Escobar I.; Jang Y.; Kim W.; Ausubel F.M.; Mylonakis E.
- Ewha Authors
- 김우성
- SCOPUS Author ID
- 김우성
- Issue Date
- 2020
- Journal Title
- International Journal of Molecular Sciences
- ISSN
- 1661-6596
- Citation
- International Journal of Molecular Sciences vol. 21, no. 21, pp. 1 - 16
- Keywords
- Caenorhabditis elegans; Immunity; Pathogenic bacteria; S1P; S1P kinase; S1P transporters; Sphingosine-1-phosphate
- Publisher
- MDPI AG
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Sphingosine-1-phophate (S1P) is a sphingolipid-derived signaling molecule that controls diverse cellular functions including cell growth, homeostasis, and stress responses. In a variety of metazoans, cytosolic S1P is transported into the extracellular space where it activates S1P receptors in a concentration-dependent manner. In the free-living nematode Caenorhabditis elegans, the spin-2 gene, which encodes a S1P transporter, is activated during Gram-positive or Gram-negative bacterial infection of the intestine. However, the role during infection of spin-2 and three additional genes in the C. elegans genome encoding other putative S1P transporters has not been elucidated. Here, we report an evolutionally conserved function for S1P and a non-canonical role for S1P transporters in the C. elegans immune response to bacterial pathogens. We found that mutations in the sphingosine kinase gene (sphk-1) or in the S1P transporter genes spin-2 or spin-3 decreased nematode survival after infection with Pseudomonas aeruginosa or Enterococcus faecalis. In contrast to spin-2 and spin-3, mutating spin-1 leads to an increase in resistance to P. aeruginosa. Consistent with these results, when wild-type C. elegans were supplemented with extracellular S1P, we found an increase in their lifespan when challenged with P. aeruginosa and E. faecalis. In comparison, spin-2 and spin-3 mutations suppressed the ability of S1P to rescue the worms from pathogen-mediated killing, whereas the spin-1 mutation had no effect on the immune-enhancing activity of S1P. S1P demonstrated no antimicrobial activity toward P. aeruginosa and Escherichia coli and only minimal activity against E. faecalis MMH594 (40 µM). These data suggest that spin-2 and spin-3, on the one hand, and spin-1, on the other hand, transport S1P across cellular membranes in opposite directions. Finally, the immune modulatory effect of S1P was diminished in C. elegans sek-1 and pmk-1 mutants, suggesting that the immunomodulatory effects of S1P are mediated by the p38 MAPK signaling pathway. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- DOI
- 10.3390/ijms21217813
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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