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Media type:
E-Article
Title:
TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ
Contributor:
Papageorgiou, Ismini E.;
Lewen, Andrea;
Galow, Lukas V.;
Cesetti, Tiziana;
Scheffel, Jörg;
Regen, Tommy;
Hanisch, Uwe-Karsten;
Kann, Oliver
imprint:
Proceedings of the National Academy of Sciences, 2016
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.1513853113
ISSN:
1091-6490;
0027-8424
Origination:
Footnote:
Description:
<jats:title>Significance</jats:title>
<jats:p>Microglia (brain macrophages) become rapidly activated in most neuropsychiatric disorders. A popular concept is that a single pathogenic stimulus, such as bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4), is sufficient to induce a reactive proinflammatory phenotype in microglia that exerts neurotoxicity. This concept is biologically risky, however. Here we provide evidence that chronic activation with either LPS or the leukocyte cytokine IFN-γ induces different reactive phenotypes in microglia of postnatal hippocampal tissue. Notably, these phenotypes only moderately alter diverse neuronal functions. In contrast, coactivation of TLR4 and IFN-γ receptors results in massive neural dysfunction and death. Thus, activation of TLR4 in microglia in situ requires concomitant IFN-γ signaling from other host immune cells to induce neurodegeneration.</jats:p>