論文 - 詳細
| RRC ID | 65300 |
|---|---|
| 著者 | Lee K, Escobar I, Jang Y, Kim W, Ausubel FM, Mylonakis E. |
| タイトル | In the Model Host Caenorhabditis elegans, Sphingosine-1-Phosphate-Mediated Signaling Increases Immunity toward Human Opportunistic Bacteria. |
| ジャーナル | Int J Mol Sci |
| 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. eleganssek-1 and pmk-1 mutants, suggesting that the immunomodulatory effects of S1P are mediated by the p38 MAPK signaling pathway. |
| 巻・号 | 21(21) |
| 公開日 | 2020-10-22 |
| DOI | 10.3390/ijms21217813 |
| PII | ijms21217813 |
| PMID | 33105563 |
| PMC | PMC7672543 |
| MeSH | Animals Anti-Bacterial Agents / pharmacology Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Caenorhabditis elegans / drug effects Caenorhabditis elegans / immunology* Caenorhabditis elegans / microbiology* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Escherichia coli / drug effects Escherichia coli / isolation & purification Escherichia coli / pathogenicity Host-Pathogen Interactions / physiology* Humans Longevity Lysophospholipids / metabolism* Lysophospholipids / pharmacology Membrane Proteins / genetics Membrane Proteins / metabolism Mutation Phosphotransferases (Alcohol Group Acceptor) / genetics Phosphotransferases (Alcohol Group Acceptor) / metabolism Pseudomonas aeruginosa / drug effects Pseudomonas aeruginosa / isolation & purification Pseudomonas aeruginosa / pathogenicity Signal Transduction Sphingosine / analogs & derivatives* Sphingosine / metabolism Sphingosine / pharmacology p38 Mitogen-Activated Protein Kinases / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1978 |