In the model host caenorhabditis elegans, sphingosine-1-phosphate-mediated signaling increases immunity toward human opportunistic bacteria

Kiho Lee, Iliana Escobar, Yeeun Jang, Wooseong Kim, Frederick M. Ausubel, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Article number7813
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Issue number21
StatePublished - 1 Nov 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • Caenorhabditis elegans
  • Immunity
  • Pathogenic bacteria
  • S1P
  • S1P kinase
  • S1P transporters
  • Sphingosine-1-phosphate


Dive into the research topics of 'In the model host caenorhabditis elegans, sphingosine-1-phosphate-mediated signaling increases immunity toward human opportunistic bacteria'. Together they form a unique fingerprint.

Cite this