{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:52:03Z","timestamp":1790232723085,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T00:00:00Z","timestamp":1218758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001207","name":"Department of Health, New South Wales Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001207","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP0557819"],"award-info":[{"award-number":["DP0557819"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p>\n                    During helminth infections, alternatively activated macrophages (AAMacs) are key to promoting Th2 responses and suppressing Thl\u2010driven inflammatory pathology. Th2 cytokines IL\u20104 and\/or IL\u201013 are believed to be important in the induction and activation of AAMacs. Using murine models for the helminth infections caused by\n                    <jats:italic>Fasciola hepatica<\/jats:italic>\n                    (Fh) and\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    (Sm), we show that a secreted antioxidant, peroxiredoxin (Prx), induces alternative activation of macrophages. These activated, Ym1\u2010expressing macrophages enhanced the secretion of IL\u20104, IL\u20105, and IL\u201013 from naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Administration of recombinant FhPrx and SmPrx to wild\u2010type and IL\u20104\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and IL\u201013\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice induced the production of AAMacs. In addition, Prx stimulated the expression of markers of AAMacs (particularly, Ym1)\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and therefore can act independently of IL\u20104\/IL\u201013 signaling. The immunomodulatory property of Prx is not due to its antioxidant activity, as an inactive recombinant variant with active site Cys residues replaced by Gly could also induce AAMacs and Th2 responses. Immunization of mice with recombinant Prx or passive transfer of anti\u2010Prx antibodies prior to infection with Fh not only blocked the induction of AAMacs but also the development of parasite\u2010specific Th2 responses. We propose that Prx activates macrophages as an initial step in the induction of Th2 responses by helminth parasites and is thereby a novel pathogen\u2010associated molecular pattern.\u2014 Donnelly, S., Stack, C. M., O'Neill, S. M., Sayed, A. A., Williams, D. L., Dalton, J. P. Helminth 2\u2010Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 4022\u20134032 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-106278","type":"journal-article","created":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T20:44:10Z","timestamp":1218833050000},"page":"4022-4032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":205,"title":["Helminth 2\u2010Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages"],"prefix":"10.1096","volume":"22","author":[{"given":"Sheila","family":"Donnelly","sequence":"first","affiliation":[{"name":"Institute for the Biotechnology of Infectious Diseases University of Technology Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin M.","family":"Stack","sequence":"additional","affiliation":[{"name":"Institute for the Biotechnology of Infectious Diseases University of Technology Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"School of Nursing Dublin City University Glasnevin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Illinois State University Normal Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Illinois State University Normal Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Dalton","sequence":"additional","affiliation":[{"name":"Institute for the Biotechnology of Infectious Diseases University of Technology Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02302-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.01.004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1451"},{"key":"e_1_2_6_5_1","first-page":"678","article-title":"Acidic mammalian chitinase in asthmatic Th2 inflammation and IL\u201013 pathway activation","volume":"304","author":"Zhu Z.","year":"2004","journal-title":"Science"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0045"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri978"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.71.4.597"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0406249"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-3-7"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(200004)30:4<1127::AID-IMMU1127>3.0.CO;2-#"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.4049\/jimmunol.163.12.6702","article-title":"Kupffer cells from Schistosoma mansoni\u2010infected mice participate in the prompt type 2 differentiation of hepatic T cells in response to worm antigens","volume":"163","author":"Hayashi N.","year":"1999","journal-title":"J. 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