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Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis

Authors :
Ine M. J. Wolfs
Erwin Wijnands
Chantal C. H. Pöttgens
David Engel
Emiel P. C. van der Vorst
Linda Beckers
Irma van Die
Pieter Goossens
Marjo M. P. C. Donners
Marion J.J. Gijbels
J. Lauran Stöger
Patrick J. van Gorp
Georg Kraal
Menno P.J. de Winther
Erik A.L. Biessen
Molecular cell biology and Immunology
CCA - Immuno-pathogenesis
Promovendi CD
Pathologie
Moleculaire Genetica
Ondersteunend personeel CD
Ondersteunend personeel NTM
RS: CARIM - R2 - Cardiac function and failure
RS: CARIM - R3 - Vascular biology
Genetica & Celbiologie
Other departments
Medical Biochemistry
ACS - Amsterdam Cardiovascular Sciences
AII - Amsterdam institute for Infection and Immunity
Source :
Wolfs, I M J, Stoger, J L, Goossens, P, Pottgens, 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 2014, ' Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis ', FASEB Journal, vol. 28, no. 1, pp. 288-299 . https://doi.org/10.1096/fj.13-235911, FASEB Journal, 28(1), 288-299. FASEB, Faseb Journal, 28(1), 288-299. FASEB, FASEB journal, 28(1), 288-299. FASEB
Publication Year :
2014

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 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-, 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., Stoger, J. L., Goossens, P., Pottgens, 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.

Details

ISSN :
08926638
Database :
OpenAIRE
Journal :
Wolfs, I M J, Stoger, J L, Goossens, P, Pottgens, 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 2014, ' Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis ', FASEB Journal, vol. 28, no. 1, pp. 288-299 . https://doi.org/10.1096/fj.13-235911, FASEB Journal, 28(1), 288-299. FASEB, Faseb Journal, 28(1), 288-299. FASEB, FASEB journal, 28(1), 288-299. FASEB
Accession number :
edsair.doi.dedup.....a5cec712b1f1d2765f4650170bf996fe
Full Text :
https://doi.org/10.1096/fj.13-235911