{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:27:46Z","timestamp":1791275266201,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic<jats:italic>Schistosoma mansoni<\/jats:italic>infection. Although infection intensities were similar in C57BL\/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4<jats:sup>+<\/jats:sup>Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.<\/jats:p>","DOI":"10.1128\/iai.74.3.1471-1479.2006","type":"journal-article","created":{"date-parts":[[2006,2,23]],"date-time":"2006-02-23T00:18:14Z","timestamp":1140653894000},"page":"1471-1479","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":174,"title":["Interleukin-5 (IL-5) Augments the Progression of Liver Fibrosis by Regulating IL-13 Activity"],"prefix":"10.1128","volume":"74","author":[{"given":"Rachael M.","family":"Reiman","sequence":"first","affiliation":[{"name":"Immunopathogenesis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Immunopathogenesis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl G.","family":"Feng","sequence":"additional","affiliation":[{"name":"Immunobiology Sections, Laboratory of Parasitic Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Hari","sequence":"additional","affiliation":[{"name":"Immunopathogenesis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Knight","sequence":"additional","affiliation":[{"name":"Immunopathogenesis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W.","family":"Cheever","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Rockville, Maryland 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene F.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Eosinophil Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Wynn","sequence":"additional","affiliation":[{"name":"Immunopathogenesis"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.3014-3018.1999"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2778"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761992000900012"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.4049\/jimmunol.153.2.753","volume":"153","year":"1994","unstructured":"Cheever, A. 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