Interferon-gamma mediates neuronal killing of intracellular bacteria.
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.
Jin
Y
Y
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Lundkvist
G
G
Dons
L
L
Kristensson
K
K
Rottenberg
M E
ME
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
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