title: Monocyte-mediated immune defense against murine Listeria monocytogenes infection.
abstract: Infection of mice with Listeria monocytogenes induces a robust innate inflammatory response that restricts bacterial growth in the liver and spleen prior to the development of protective T cell responses. Ly6C(hi) monocytes contribute to the innate immune response following L. monocytogenes infection and in their absence, mice rapidly succumb to infection. Emigration of Ly6C(hi) monocytes from the bone marrow into the circulation is the first step in their recruitment to sites of L. monocytogenes infection and is triggered by CCL2- and CCL7-mediated stimulation of CCR2 chemokine receptors on monocytes. CCL2 expression by mesenchymal stem cells in the bone marrow, in response to TLR stimulation, drives monocyte emigration from cellular compartments into vascular sinuses of the bone marrow. In addition to TLR ligands, type I interferon-mediated signals can also drive monocyte emigration from the bone marrow during L. monocytogenes infection. Once Ly6C(hi) monocytes enter the bloodstream, trafficking to sites of infection in the liver and spleen is CCR2 independent. In the liver, CD11b on the monocyte and ICAM-1 on the surface of endothelial cells target Ly6C(hi) monocytes to foci of L. monocytogenes infection. At the site of infection, Ly6C(hi) monocytes undergo MyD88-dependent differentiation into TNF and iNOS-producing dendritic cells (TipDCs) and express MHC class II, B7.1, and CD40 on their cell surface. How TipDCs mediate bacterial clearance during early L. monocytogenes infection remains an active area of investigation.
authors.affiliation: Infectious Diseases Service, Department of Medicine, Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: Natalya V
authors.initials: NV
authors.lastname: Serbina
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction
chemical_list: D016207:Cytokines