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Their prolonged intestinal infections persist despite intact immune systems of their hosts and are attributed to immunomodulatory activities of their secretions. The p43 (Tm-DLP-1) protein of\n                    <jats:italic>Trichuris muris<\/jats:italic>\n                    of mice comprises 95% of the protein secreted by adult parasites, binds matrix proteoglycans, and has immune cytokine (IL-13)-neutralising activity. Using fluorescence-based methods we show that p43 binds fatty acids and retinol, including signalling lipids or precursors thereof. The orthologue of p43 from the human whipworm,\n                    <jats:italic>Trichuris trichiura,<\/jats:italic>\n                    exhibits similar lipid-binding activity. From the known molecular structure of p43, we explore the existence of extensive surface-accessible cavities with diverse surface charge characteristics which may indicate binding of diverse small molecule types, and its internally duplicated subdomains likely possess divergent characteristics. p43 represents a novel protein type (\u201cdorylipophorin\u201d) only known in Dorylaimia (Clade I) nematodes. We demonstrate that p43 is the dominant protein in\n                    <jats:italic>Trichuris\u2019s<\/jats:italic>\n                    pseudocoelomic fluid, replacing the major internal lipid transporters of all other nematode clades, representing an ancient functional dichotomy. In\n                    <jats:italic>Trichuris<\/jats:italic>\n                    , and potentially other Clade I parasites of plants and animals, these proteins\u2019 lipid-binding activities may be adapted for both internal physiological and external immunomodulatory activities.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-08124-w","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T03:53:08Z","timestamp":1751946788000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The immunomodulatory p43 secreted protein of Trichuris whipworm parasites is a lipid carrier that binds signalling lipids and precursors"],"prefix":"10.1038","volume":"15","author":[{"given":"Malcolm W.","family":"Kennedy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison J.","family":"Bancroft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K.","family":"Grencis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"8124_CR1","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1017\/s0031182021000846","volume":"148","author":"AJ Bancroft","year":"2021","unstructured":"Bancroft, A. 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