title: Listeria monocytogenes-infected bone marrow myeloid cells promote bacterial invasion of the central nervous system.
abstract: Listeria monocytogenes is a facultative intracellular pathogen that is able to invade the central nervous system causing meningoencephalitis and brain abscesses. The mechanisms allowing bacteria to cross the blood-brain barrier are poorly understood. In this work, we used an experimental model of acute listeriosis in the mouse inducing a reproducible invasion of the central nervous system. At the early phase of infection, we find that bacteria invade and rapidly grow in bone marrow cells identified as bone marrow myelomonocytic cells expressing the phenotype CD31pos:Ly-6Cpos:CD11b(pos):LY-6Glow. We demonstrate that central nervous system invasion is facilitated by injecting L. monocytogenes-infected bone marrow cells in comparison with free bacteria or infected spleen cells. In mice transplanted with bone marrow cells from transgenic donor mice expressing the green fluorescent protein (GFP), we show that infected myeloid GFP+ cells adhere to activated brain endothelial cells, accumulate in brain vessels and participate to the pathogenesis of meningoencephalitis and brain abscesses. Our results demonstrate that bone marrow, the main haematopoietic tissue, is a previously unrecognized reservoir of L. monocytogenes-infected myeloid cells, which can play a crucial role in the pathophysiology of meningoencephalitis by releasing infected cells into the circulation that ultimately invade the central nervous system.
authors.affiliation: INSERM U-570, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
authors.forename: Olivier F
authors.initials: OF
authors.lastname: Join-Lambert
authors.forename: Sophie
authors.initials: S
authors.lastname: Ezine
authors.forename: Alban
authors.initials: A
authors.lastname: Le Monnier
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Patrick
authors.initials: P
authors.lastname: Berche
authors.forename: Samer
authors.initials: S
authors.lastname: Kayal
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001853:Bone Marrow / Q000382:microbiology; D018845:CD11 Antigens / Q000032:analysis; D002490:Central Nervous System / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D016130:Immunophenotyping; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000382:microbiology* / Q000473:pathology; D008584:Meningitis, Listeria / Q000382:microbiology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000382:microbiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D013194:Staining and Labeling
chemical_list: D000950:Antigens, Ly; D018845:CD11 Antigens; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins