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Reprogramming macrophages to an anti‐inflammatory phenotype by helminth antigens reduces murine atherosclerosis
Author(s) -
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.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-235911
Subject(s) - inflammation , proinflammatory cytokine , macrophage , immune system , immunology , antigen , bone marrow , monocyte , biology , biochemistry , in vitro
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 Ly6C high 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