{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:49:08Z","timestamp":1791136148749,"version":"4.1.0"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"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":[[2009,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The prime function of classically activated macrophages (activated by Th1-type signals, such as IFN-\u03b3) is microbial destruction. Alternatively activated macrophages (activated by Th2 cytokines, such as IL-4 and IL-13) play important roles in allergy and responses to helminth infection. We utilize a murine model of filarial infection, in which adult nematodes are surgically implanted into the peritoneal cavity of mice, as an in vivo source of alternatively activated macrophages. At 3 wk postinfection, the peritoneal exudate cell population is dominated by macrophages, termed nematode-elicited macrophages (NeM\u03c6), that display IL-4-dependent features such as the expression of arginase 1, RELM-\u03b1 (resistin-like molecule \u03b1), and Ym1. Since increasing evidence suggests that macrophages show functional adaptivity, the response of NeM\u03c6 to proinflammatory Th1-activating signals was investigated to determine whether a switch between alternative and classical activation could occur in macrophages differentiated in an in vivo infection setting. Despite the long-term exposure to Th2 cytokines and antiinflammatory signals in vivo, we found that NeM\u03c6 were not terminally differentiated but could develop a more classically activated phenotype in response to LPS and IFN-\u03b3. This was reflected by a switch in the enzymatic pathway for arginine metabolism from arginase to inducible NO synthase and the reduced expression of RELM-\u03b1 and Ym1. Furthermore, this enabled NeM\u03c6 to become antimicrobial, as LPS\/IFN-\u03b3-treated NeM\u03c6 produced NO that mediated killing of Leishmania mexicana. However, the adaptation to antimicrobial function did not extend to key regulatory pathways, such as IL-12 production, which remained unaltered.<\/jats:p>","DOI":"10.4049\/jimmunol.0803463","type":"journal-article","created":{"date-parts":[[2009,2,20]],"date-time":"2009-02-20T22:41:32Z","timestamp":1235169692000},"page":"3084-3094","source":"Crossref","is-referenced-by-count":112,"title":["Alternatively Activated Macrophages Elicited by Helminth Infection Can Be Reprogrammed to Enable Microbial Killing"],"prefix":"10.1093","volume":"182","author":[{"given":"Katie J","family":"Mylonas","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera G","family":"Nair","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Prieto-Lafuente","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Paape","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E","family":"Allen","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"2025032622233278900_R1","first-page":"23","article-title":"Alternative activation of macrophages.","volume-title":"Nat. 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