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

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-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.

• Authors: Ine M J Wolfs, J Lauran Stöger, Pieter Goossens, Chantal Pöttgens, Marion J J Gijbels, Erwin Wijnands, Emiel P C van der Vorst, Patrick van Gorp, Linda Beckers, David Engel, Erik A L Biessen, Georg Kraal, Irma van Die, Marjo M P C Donners, Menno P J de Winther
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 28 Issue 1 Pg. 288-99 (Jan 2014) ISSN: 1530-6860 [Electronic] United States
• PMID: 24043262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Helminth
• Chemokine CCL2
• Receptors, LDL
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antigens, Helminth (metabolism)
• Atherosclerosis (metabolism, therapy)
• Chemokine CCL2 (metabolism)
• Macrophages (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Receptors, LDL (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)