title: Macrophage Polarization during Murine Lyme Borreliosis.
abstract: Infection of C3H mice with Borrelia burgdorferi, the causative agent of Lyme disease, reliably produces an infectious arthritis and carditis that peak around 3 weeks postinfection and then spontaneously resolve. Macrophage polarization has been suggested to drive inflammation, the clearance of bacteria, and tissue repair and resolution in a variety of infectious disease models. During Lyme disease it is clear that macrophages are capable of clearing Borrelia spirochetes and exhausted neutrophils; however, the role of macrophage phenotype in disease development or resolution has not been studied. Using classical (NOS2) and alternative (CD206) macrophage subset-specific markers, we determined the phenotype of F4/80(+) macrophages within the joints and heart throughout the infection time course. Within the joint, CD206(+) macrophages dominated throughout the course of infection, and NOS2(+) macrophage numbers became elevated only during the peak of inflammation. We also found dual NOS2(+) CD206(+) macrophages which increased during resolution. In contrast to findings for the ankle joints, numbers of NOS2(+) and CD206(+) macrophages in the heart were similar at the peak of inflammation. 5-Lipoxygenase-deficient (5-LOX(-/-)) mice, which display a failure of Lyme arthritis resolution, recruited fewer F4/80(+) cells to the infected joints and heart, but macrophage subset populations were unchanged. These results highlight differences in the inflammatory infiltrates during Lyme arthritis and carditis and demonstrate the coexistence of multiple macrophage subsets within a single inflammatory site.
authors: Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
authors: Carrie E
authors: CE
authors: Lasky
authors: Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
authors: Rachel M
authors: RM
authors: Olson
authors: Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA brownchar@missouri.edu.
authors: Charles R
authors: CR
authors: Brown
mesh_terms: D000818:Animals; D025065:Borrelia burgdorferi / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D016130:Immunophenotyping; D007596:Joints / Q000473:pathology; D037181:Lectins, C-Type / Q000032:analysis; D008193:Lyme Disease / Q000276:immunology*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000502:physiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse