title: The adult murine heart has a sparse, phagocytically active macrophage population that expands through monocyte recruitment and adopts an 'M2' phenotype in response to Th2 immunologic challenge.
abstract: Tissue resident macrophages have vital homeostatic roles in many tissues but their roles are less well defined in the heart. The present study aimed to identify the density, polarisation status and distribution of macrophages in the healthy murine heart and to investigate their ability to respond to immune challenge. Histological analysis of hearts from CSF-1 receptor (csf1-GFP; MacGreen) and CX3CR1 (Cx3cr1(GFP/+)) reporter mice revealed a sparse population of GFP positive macrophages that were evenly distributed throughout the left and right ventricular free walls and septum. F4/80+CD11b+ cardiac macrophages, sorted from myocardial homogenates, were able to phagocytose fluorescent beads in vitro and expressed markers typical of both 'M1' (IL-1β, TNF and CCR2) and 'M2' activation (Ym1, Arg 1, RELMα and IL-10), suggesting no specific polarisation in healthy myocardium. Exposure to Th2 challenge by infection of mice with helminth parasites Schistosoma mansoni, or Heligmosomoides polygyrus, resulted in an increase in cardiac macrophage density, adoption of a stellate morphology and increased expression of Ym1, RELMα and CD206 (mannose receptor), indicative of 'M2' polarisation. This was dependent on recruitment of Ly6ChighCCR2+ monocytes and was accompanied by an increase in collagen content. In conclusion, in the healthy heart resident macrophages are relatively sparse and have a phagocytic role. Following Th2 challenge this population expands due to monocyte recruitment and adopts an 'M2' phenotype associated with increased tissue fibrosis.
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute (QMRI), University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom. Electronic address: kmylonas@staffmail.ed.ac.uk.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Mylonas
authors.affiliation: Centre for Inflammation Research, QMRI, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Jenkins
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute (QMRI), University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom.
authors.forename: Raphael F P
authors.initials: RF
authors.lastname: Castellan
authors.affiliation: Institute of Immunology and Infection Research (IIIR), The King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, Scotland, United Kingdom.
authors.forename: Dominik
authors.initials: D
authors.lastname: Ruckerl
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute (QMRI), University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom.
authors.forename: Kieran
authors.initials: K
authors.lastname: McGregor
authors.affiliation: Institute of Immunology and Infection Research (IIIR), The King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, Scotland, United Kingdom; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Grafton Street, Manchester M13 9NT, England, United Kingdom.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Phythian-Adams
authors.affiliation: Institute of Immunology and Infection Research (IIIR), The King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, Scotland, United Kingdom.
authors.forename: James P
authors.initials: JP
authors.lastname: Hewitson
authors.affiliation: Institute of Immunology and Infection Research (IIIR), The King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, Scotland, United Kingdom.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Campbell
authors.affiliation: Institute of Immunology and Infection Research (IIIR), The King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, Scotland, United Kingdom; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Grafton Street, Manchester M13 9NT, England, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
authors.affiliation: Institute of Immunology and Infection Research (IIIR), The King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, Scotland, United Kingdom.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allen
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute (QMRI), University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Gray
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D049452:Green Fluorescent Proteins / Q000235:genetics; D006321:Heart / Q000469:parasitology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D037102:Lectins / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology*; D009351:Nematospiroides dubius / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000235:genetics; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology; D001619:beta-N-Acetylhexosaminidases / Q000096:biosynthesis
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; C413576:Retnla protein, mouse; C036763:monocyte-macrophage differentiation antigen; D049452:Green Fluorescent Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases
keywords: Heart; Helminth infection; Macrophage