A Trichuris whipworm parasite releases its p43 immunomodulatory protein loaded with selected bioactive lipid mediators

The p43 (Tm-DLP-1) protein secreted by the murine whipworm Trichuris muris binds matrix proteoglycans and interacts with IL-13, the combined effects of which likely mediates the chronic infection by these parasites. In fluorescence-based competition experiments we recently showed that p43 and its orthologue in the whipworm of humans, Trichuris trichiura, both bind fatty acids including the precursors of signalling lipids important in immune and inflammatory reactions. In this context there is a difference between those ligands a protein may bind in such experiments and those present in the protein directly secreted by the parasites. We here report, using solvent extraction and liquid chromatography–mass spectrometry, that native p43 secreted into serum-free media by adult T. muris worms contains precursors of signalling lipids eicosapentaenoic acid, docosahexaenoic acid, and the bioactive 5,6-epoxyeicosatrienoic acid (5.6-EET), and 15-hydroxyeicosatetraenoic acids (15-HETE) that could contribute to p43’s potent immunomodulatory activity. Several types of lipid-binding protein released by parasitic nematodes have been shown to have immunomodulatory activities, but this is the first time that such a protein has been found to be released by the parasites already loaded with bioactive lipids.