{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T21:13:12Z","timestamp":1772658792138,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2001,7,1]],"date-time":"2001-07-01T00:00:00Z","timestamp":993945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parasite survival and host health may depend on the ability of the parasite to modulate the host immune response by the release of immunomodulatory molecules. Excretory-secretory (ES)-62, one such well-defined molecule, is a major secreted protein of the rodent filarial nematode Acanthocheilonema viteae, and has homologues in human filarial nematodes. Previously we have shown that ES-62 is exclusively associated with a Th2 Ab response in mice. Here we provide a rationale for this polarized immune response by showing that the parasite molecule suppresses the IFN-\u03b3\/LPS-induced production, by macrophages, of bioactive IL-12 (p70), a key cytokine in the development of Th1 responses. This suppression of the induction of a component of the host immune response extends to the production of the proinflammatory cytokines IL-6 and TNF-\u03b1, but not NO. The molecular mechanism underlying these findings awaits elucidation but, intriguingly, the initial response of macrophages to ES-62 is to demonstrate a low and transient release of these cytokines before becoming refractory to further release induced by IFN-\u03b3\/LPS. The relevance of our observations is underscored by the finding that macrophages recovered from mice exposed to \u201cphysiological\u201d levels of ES-62 by the novel approach of continuous release from implanted osmotic pumps in vivo were similarly refractory to release of IL-12, TNF-\u03b1, IL-6, but not NO, ex vivo. Therefore, our results suggest that exposure to ES-62 renders macrophages subsequently unable to produce Th1\/proinflammatory cytokines. This likely contributes to the generation of immune responses with an anti-inflammatory Th2 phenotype, a well-documented feature of filarial nematode infection.<\/jats:p>","DOI":"10.4049\/jimmunol.167.2.940","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T22:17:55Z","timestamp":1398118675000},"page":"940-945","source":"Crossref","is-referenced-by-count":99,"title":["Modulation of Macrophage Cytokine Production by ES-62, a Secreted Product of the Filarial Nematode\n                    <i>Acanthocheilonema viteae<\/i>"],"prefix":"10.1093","volume":"167","author":[{"given":"Helen S","family":"Goodridge","sequence":"first","affiliation":[{"name":"Department of Immunology and Bacteriology, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma H","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Harnett","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Strathclyde , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol C","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Immunology and Bacteriology, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret M","family":"Harnett","sequence":"additional","affiliation":[{"name":"Department of Immunology and Bacteriology, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Foo Y","family":"Liew","sequence":"additional","affiliation":[{"name":"Department of Immunology and Bacteriology, University of Glasgow , Glasgow ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,7,15]]},"reference":[{"key":"2026020209104284000_R1","volume-title":"Filariasis","year":"2000"},{"key":"2026020209104284000_R2","first-page":"119","volume-title":"Trans. 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