title: 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.affiliation: 1Department of Medical Biochemistry, Rm. L01-146.2, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.dewinther@amc.uva.nl.
authors.forename: Ine M J
authors.initials: IM
authors.lastname: Wolfs
authors.forename: J Lauran
authors.initials: JL
authors.lastname: Stöger
authors.forename: Pieter
authors.initials: P
authors.lastname: Goossens
authors.forename: Chantal
authors.initials: C
authors.lastname: Pöttgens
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Erwin
authors.initials: E
authors.lastname: Wijnands
authors.forename: Emiel P C
authors.initials: EP
authors.lastname: van der Vorst
authors.forename: Patrick
authors.initials: P
authors.lastname: van Gorp
authors.forename: Linda
authors.initials: L
authors.lastname: Beckers
authors.forename: David
authors.initials: D
authors.lastname: Engel
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
authors.forename: Georg
authors.initials: G
authors.lastname: Kraal
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
authors.forename: Marjo M P C
authors.initials: MM
authors.lastname: Donners
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000628:therapy*; D018932:Chemokine CCL2 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D018932:Chemokine CCL2; D011973:Receptors, LDL; D014409:Tumor Necrosis Factor-alpha
keywords: immune modulation; inflammation; monocytes; mouse; schistosome