title: Interferon-gamma mediates neuronal killing of intracellular bacteria.
abstract: Neurons can be targets for microbes, which could kill the neurons. Just in reverse, we, in this study, report that bacteria can be killed when entering a neuron. Primary cultures of foetal mouse hippocampal neurons and a neuronal cell line derived from mouse hypothalamus were infected by Listeria monocytogenes. Treatment with interferon-gamma (IFN-gamma) did not affect bacterial uptake, but resulted in increased killing of intracellular bacteria, whereas the neuronal cell remained intact. The IFN-gamma-mediated bacterial killing was mapped to the neuronal cytosol, before listerial actin tail formation. Treatment with IFN-gamma induced phosphorylation of the transcription factor STAT-1 in neurons and IFN-gamma-mediated listerial killing was not observed in STAT-1(-/-) neurons or neurons treated with IFN regulatory factor-1 antisense oligonucleotides. IFN-gamma-treated neuronal cells showed increased levels of inducible nitric oxide synthase (iNOS) mRNA, and antisense iNOS oligonucleotides hampered the bacterial killing by neurons upon IFN-gamma treatment. This novel neuronal function - i.e., that of a microbe killer - could play a crucial role in the control of infections in the immuno-privileged nervous system.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: G
authors.initials: G
authors.lastname: Lundkvist
authors.forename: L
authors.initials: L
authors.lastname: Dons
authors.forename: K
authors.initials: K
authors.lastname: Kristensson
authors.forename: M E
authors.initials: ME
authors.lastname: Rottenberg
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D008088:Listeriosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010750:Phosphoproteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse