title: Dissociation of innate immune responses in microglia infected with Listeria monocytogenes.
abstract: Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. Here, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. Whereas the bacterial gene hly seems responsible for both transcriptional programmes in macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)-regulated transcriptional programme. Listeria also represses in microglia the late immune response gathered in two clusters, microbial degradation, and interferon (IFN)-inducible genes. The bacterial gene actA was required in microglia to induce TNF-regulated responses and to repress the late response. Isolation of microglial phagosomes revealed a phagosomal environment unable to destroy Listeria. Microglial phagosomes were also defective in several signaling and trafficking components reported as relevant for Listeria innate immune responses. This transcriptional strategy in microglia induced high levels of TNF-α and monocyte chemotactic protein-1 and low production of other neurotoxic compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. These cytokines and toxic microglial products are also released by primary microglia, and this cytokine and chemokine cocktail display a low potential to trigger neuronal apoptosis. This overall bacterial strategy strongly suggests that microglia limit Listeria inflammation pattern exclusively through TNF-mediated responses to preserve brain integrity.
authors: Grupo de Genómica, Proteómica y vacunas, Instituto de Investigación y Formación Marqués de Valdecilla (IFIMAV), Primera Planta-Laboratorio 124, Avda. de Cardenal Herrera Oria, s/n, 39011, Santander, Spain.
authors: Elisabet
authors: E
authors: Frande-Cabanes
authors: Lorena
authors: L
authors: Fernandez-Prieto
authors: Ricardo
authors: R
authors: Calderon-Gonzalez
authors: Estela
authors: E
authors: Rodríguez-Del Río
authors: Sonsoles
authors: S
authors: Yañez-Diaz
authors: Monica
authors: M
authors: López-Fanarraga
authors: Carmen
authors: C
authors: Alvarez-Domínguez
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008088:Listeriosis / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha
keywords: cytokines; listeriosis; macrophages; microglia; neuronal cell death