Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis
Atherosclerosis is a lipid‐driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth‐derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis...
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| creator | Wolfs, Ine M. J. Stöger, J. Lauran Goossens, Pieter Pöttgens, Chantal Gijbels, Marion J. J. Wijnands, Erwin Vorst, Emiel P. C. Gorp, Patrick Beckers, Linda Engel, David Biessen, Erik A. L. Kraal, Georg Die, Irma Donners, Marjo M. P. C. Winther, Menno P. J. |
| description | Atherosclerosis is a lipid‐driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth‐derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow‐derived macrophages, SEAs induce anti‐inflammatory macrophages, typified by high levels of IL‐10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR‐/‐ mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS‐injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T‐lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6Chigh monocytes, and macrophages showed high IL‐10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA‐treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF‐α, monocyte chemotactic protein 1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth‐derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.—Wolfs, I. M. J., Stöger, J. L., Goossens, P., Pöttgens, C., Gijbels, M. J. J., Wijnands, E., van der Vorst, E. P. C., van Gorp, P., Beckers, L., Engel, D., Biessen, E. A. L., Kraal, G., van Die, I., Donners, M. M. P. C., de Winther, M. P. J. Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis. FASEB J. 28, 288–299 (2014). www.fasebj.org |
| doi_str_mv | 10.1096/fj.13-235911 |
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J. ; Stöger, J. Lauran ; Goossens, Pieter ; Pöttgens, Chantal ; Gijbels, Marion J. J. ; Wijnands, Erwin ; Vorst, Emiel P. C. ; Gorp, Patrick ; Beckers, Linda ; Engel, David ; Biessen, Erik A. L. ; Kraal, Georg ; Die, Irma ; Donners, Marjo M. P. C. ; Winther, Menno P. J.</creator><creatorcontrib>Wolfs, Ine M. J. ; Stöger, J. Lauran ; Goossens, Pieter ; Pöttgens, Chantal ; Gijbels, Marion J. J. ; Wijnands, Erwin ; Vorst, Emiel P. C. ; Gorp, Patrick ; Beckers, Linda ; Engel, David ; Biessen, Erik A. L. ; Kraal, Georg ; Die, Irma ; Donners, Marjo M. P. C. ; Winther, Menno P. J.</creatorcontrib><description>Atherosclerosis is a lipid‐driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth‐derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow‐derived macrophages, SEAs induce anti‐inflammatory macrophages, typified by high levels of IL‐10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR‐/‐ mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS‐injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T‐lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6Chigh monocytes, and macrophages showed high IL‐10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA‐treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF‐α, monocyte chemotactic protein 1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth‐derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.—Wolfs, I. M. J., Stöger, J. L., Goossens, P., Pöttgens, C., Gijbels, M. J. J., Wijnands, E., van der Vorst, E. P. C., van Gorp, P., Beckers, L., Engel, D., Biessen, E. A. L., Kraal, G., van Die, I., Donners, M. M. P. C., de Winther, M. P. J. Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis. 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J.</creatorcontrib><creatorcontrib>Stöger, J. Lauran</creatorcontrib><creatorcontrib>Goossens, Pieter</creatorcontrib><creatorcontrib>Pöttgens, Chantal</creatorcontrib><creatorcontrib>Gijbels, Marion J. J.</creatorcontrib><creatorcontrib>Wijnands, Erwin</creatorcontrib><creatorcontrib>Vorst, Emiel P. C.</creatorcontrib><creatorcontrib>Gorp, Patrick</creatorcontrib><creatorcontrib>Beckers, Linda</creatorcontrib><creatorcontrib>Engel, David</creatorcontrib><creatorcontrib>Biessen, Erik A. L.</creatorcontrib><creatorcontrib>Kraal, Georg</creatorcontrib><creatorcontrib>Die, Irma</creatorcontrib><creatorcontrib>Donners, Marjo M. P. C.</creatorcontrib><creatorcontrib>Winther, Menno P. J.</creatorcontrib><title>Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Atherosclerosis is a lipid‐driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth‐derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow‐derived macrophages, SEAs induce anti‐inflammatory macrophages, typified by high levels of IL‐10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR‐/‐ mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS‐injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T‐lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6Chigh monocytes, and macrophages showed high IL‐10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA‐treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF‐α, monocyte chemotactic protein 1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth‐derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.—Wolfs, I. M. J., Stöger, J. L., Goossens, P., Pöttgens, C., Gijbels, M. J. J., Wijnands, E., van der Vorst, E. P. C., van Gorp, P., Beckers, L., Engel, D., Biessen, E. A. L., Kraal, G., van Die, I., Donners, M. M. P. C., de Winther, M. P. J. Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis. FASEB J. 28, 288–299 (2014). www.fasebj.org</description><subject>Animals</subject><subject>Antigens, Helminth - metabolism</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - therapy</subject><subject>Chemokine CCL2 - metabolism</subject><subject>immune modulation</subject><subject>inflammation</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Mutant Strains</subject><subject>monocytes</subject><subject>mouse</subject><subject>Receptors, LDL - genetics</subject><subject>Receptors, LDL - metabolism</subject><subject>schistosome</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctKxDAUhoMoOo7uXEuXLuyYe5ulDt5AELysQyY9nXbobZIW6c5H8Bl9EjOOuhQOOZsvP_zfQeiE4BnBSl7kqxlhMWVCEbKDJkQwHMtU4l00wamisZQsPUCH3q8wxgQTuY8OKMecUUknaP0EnWuXztR12Syj2ljXdoVZgo_6NjJNmL78fP8om7wKjOlbN0ZdAU3bjx1EizEqoApf--KbXELjIwfZYENAPbiygcj0BbjW22rzlv4I7eWm8nD8s6fo9eb6ZX4XPzze3s8vH2LLOUtjxUMHwk2acSuItTJXTKlMWGGpWuSJ4GYhEkIBM2JBUJ4YkxuumMwEJFywKTrb5oZ-6wF8r-vSW6gq00A7eE24wknQhmlAz7doKO-9g1x3rqyNGzXBeiNZ5ytNmN5KDvjpT_KwqCH7g3-tBiDZAm9lBeO_Yfrm-Ypimm5OQ1P2BZDAivs</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Wolfs, Ine M. J.</creator><creator>Stöger, J. Lauran</creator><creator>Goossens, Pieter</creator><creator>Pöttgens, Chantal</creator><creator>Gijbels, Marion J. J.</creator><creator>Wijnands, Erwin</creator><creator>Vorst, Emiel P. C.</creator><creator>Gorp, Patrick</creator><creator>Beckers, Linda</creator><creator>Engel, David</creator><creator>Biessen, Erik A. L.</creator><creator>Kraal, Georg</creator><creator>Die, Irma</creator><creator>Donners, Marjo M. P. C.</creator><creator>Winther, Menno P. J.</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201401</creationdate><title>Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis</title><author>Wolfs, Ine M. J. ; Stöger, J. Lauran ; Goossens, Pieter ; Pöttgens, Chantal ; Gijbels, Marion J. J. ; Wijnands, Erwin ; Vorst, Emiel P. C. ; Gorp, Patrick ; Beckers, Linda ; Engel, David ; Biessen, Erik A. L. ; Kraal, Georg ; Die, Irma ; Donners, Marjo M. P. C. ; Winther, Menno P. 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J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2014-01</date><risdate>2014</risdate><volume>28</volume><issue>1</issue><spage>288</spage><epage>299</epage><pages>288-299</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Atherosclerosis is a lipid‐driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth‐derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow‐derived macrophages, SEAs induce anti‐inflammatory macrophages, typified by high levels of IL‐10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR‐/‐ mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS‐injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T‐lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6Chigh monocytes, and macrophages showed high IL‐10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA‐treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF‐α, monocyte chemotactic protein 1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth‐derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.—Wolfs, I. M. J., Stöger, J. L., Goossens, P., Pöttgens, C., Gijbels, M. J. J., Wijnands, E., van der Vorst, E. P. C., van Gorp, P., Beckers, L., Engel, D., Biessen, E. A. L., Kraal, G., van Die, I., Donners, M. M. P. C., de Winther, M. P. J. Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis. FASEB J. 28, 288–299 (2014). www.fasebj.org</abstract><cop>Bethesda, MD, USA</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>24043262</pmid><doi>10.1096/fj.13-235911</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, Helminth - metabolism Atherosclerosis - metabolism Atherosclerosis - therapy Chemokine CCL2 - metabolism immune modulation inflammation Macrophages - metabolism Mice Mice, Inbred C57BL Mice, Mutant Strains monocytes mouse Receptors, LDL - genetics Receptors, LDL - metabolism schistosome Tumor Necrosis Factor-alpha - metabolism |
| title | Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis |
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