{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:07:29Z","timestamp":1787807249830,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T00:00:00Z","timestamp":1166140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p> <jats:italic>Modulation of macrophage\/dendritic cell (DC) cytokine production by the filarial nematode phosphorylcholine (PC)\u2010containing product, ES\u201062, is mediated by Toll\u2010like receptor (TLR) 4 and signal transduction depends on the TLR adaptor MyD88. Intriguingly, comparison of TLR4 knock\u2010out (ko) mice with TLR4 mutant C3H\/HeJ mice indicates that ES\u201062 cytokine responses are not dependent on the Pro712 residue of TLR4, which is crucial for the response to bacterial lipopolysaccharide (LPS). Because other immunomodulatory effects of ES\u201062 have been attributed to PC we have now investigated, using PC conjugated to ovalbumin (PC\u2010Ova), whether PC is responsible for the interaction of ES\u201062 with TLR4. PC\u2010Ova mimicked the modulation of interleukin (IL)\u201012 production by ES\u201062 in a TLR4\u2010 and MyD88\u2010dependent manner and as with native ES\u201062, PC\u2010Ova effects were not dependent on Pro712. Furthermore, both native ES\u201062 and PC\u2010Ova suppressed Akt phosphorylation, whereas neither altered the activation of p38 or Erk MAP kinases. To rule out any role for the ES\u201062 protein component, we tested a PC\u2010free recombinant ES\u201062 (rES\u201062) generated in the yeast<\/jats:italic> Pichia pastoris<jats:italic>. Surprisingly, rES\u201062 also modulated IL\u201012 production, but in a TLR4\/MyD88\u2010independent manner. Furthermore, rES\u201062 strongly activated both the p38 and Erk MAP kinases and Akt. However, recent biophysical analysis suggests there are differences in folding\/shape between native and rES\u201062 and hence data obtained with the latter should be treated with caution. Nevertheless, although our study indicates that PC is likely to be primarily responsible for the modulation of cytokine production observed with native ES\u201062, an immunomodulatory role for the protein component cannot be ruled out.<\/jats:italic><\/jats:p>","DOI":"10.1111\/j.1365-3024.2006.00926.x","type":"journal-article","created":{"date-parts":[[2006,12,16]],"date-time":"2006-12-16T02:48:20Z","timestamp":1166237300000},"page":"127-137","source":"Crossref","is-referenced-by-count":80,"title":["Phosphorylcholine mimics the effects of ES\u201062 on macrophages and dendritic cells"],"prefix":"10.1111","volume":"29","author":[{"given":"H. S.","family":"GOODRIDGE","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"McGUINESS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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