The whipworm (Trichuris suis) secretes prostaglandin E2 to suppress proinflammatory properties in human dendritic cells.
Clinical trials have shown that administration of the nematode Trichuris suis can be beneficial in treating various immune disorders. To provide insight into the mechanisms by which this worm suppresses inflammatory responses, an active component was purified from T. suis soluble products (TsSPs) that suppress---- TNF and IL-12 secretion from LPS-activated human dendritic cells (DCs). Analysis by liquid chromatography tandem mass spectrometry identified this compound as prostaglandin (PG)E2. The purified compound showed similar properties compared with TsSPs and commercial PGE2 in modulating LPS-induced expression of many cytokines and chemokines and in modulating Rab7B and P2RX7 expression in human DCs. Furthermore, the TsSP-induced reduction of TNF secretion from DCs is reversed by receptor antagonists for EP2 and EP4, indicating PGE2 action. T. suis secretes extremely high amounts of PGE2 (45-90 ng/mg protein) within their excretory/secretory products but few related lipid mediators as established by metabololipidomic analysis. Culture of T. suis with several cyclooxygenase (COX) inhibitors that inhibit mammalian prostaglandin synthesis affected the worm's motility but did not inhibit PGE2 secretion, suggesting that the worms can synthesize PGE2 via a COX-independent pathway. We conclude that T. suis secretes PGE2 to suppress proinflammatory responses in human DCs, thereby modulating the host's immune response.-Laan, L. C., Williams, A. R., Stavenhagen, K., Giera, M., Kooij, G., Vlasakov, I., Kalay, H., Kringel, H., Nejsum, P., Thamsborg, S. M., Wuhrer, M., Dijkstra, C. D., Cummings, R. D., van Die, I. The whipworm (Trichuris suis) secretes prostaglandin E2 to suppress proinflammatory properties in human dendritic cells.
Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands.
Lisa C
LC
Laan
Section for Parasitology, Health, and Development, Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
Andrew R
AR
Williams
Division of BioAnalytical Chemistry, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.|Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Kathrin
K
Stavenhagen
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Martin
M
Giera
Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands.|Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; and.
Gijs
G
Kooij
Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; and.
Iliyan
I
Vlasakov
Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands.
Hakan
H
Kalay
Section for Parasitology, Health, and Development, Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
Helene
H
Kringel
Section for Parasitology, Health, and Development, Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
Peter
P
Nejsum
Section for Parasitology, Health, and Development, Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
Stig M
SM
Thamsborg
Division of BioAnalytical Chemistry, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.|Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Manfred
M
Wuhrer
Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands.
Christine D
CD
Dijkstra
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School Center for Glycosciences, Boston, Massachusetts, USA.
Richard D
RD
Cummings
Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands; im.vandie@vumc.nl.
Irma
I
van Die
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D015394:Molecular Structure; D013045:Species Specificity; D014258:Trichuris / Q000378:metabolism*
D008070:Lipopolysaccharides; D015232:Dinoprostone
helminth therapy; immune regulation; inflammatory bowel disease; lipids; multiple sclerosis