Journal
VIROLOGY
Volume 287, Issue 1, Pages 163-170Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/viro.2001.1029
Keywords
interleukin-18; microglia; macrophages; Iba1; interferon-gamma; influenza virus; neuron; brain; apoptosis; neurodegeneration
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Knockout of the inerleukin-18 (IL-18) gene predisposed mice to impaired clearance of neurovirulent influenza A virus-infected neurons from the brain. In wild-type mice, IL-18 molecule-producing microglia/macrophages emerged in virally attacked regions as early as day 3 after infection. Microglial transformation into macrophages culminated at day 7 to 9, with upregulated expression of Iba1, a novel calcium-binding protein that controls phagocytic functions of microglia/macrophages. In IL-18-/- mice, microglial transformation was interrupted with reduced Iba1 expression. Interferon-gamma (IFN-gamma )immunopositive neurons appeared in and around virally invaded regions in wild-type mice, peaking in number at day 7, whereas such cells were barely detected in IL-18-/- mice. Stereotaxic microinjection of recombinant IFN-gamma triggered microglial transformation in IL-18-/- mice and upregulated Iba1 expression, leading to effective eradication of virally infected neurons. Collectively, these results suggest that IL-18 plays a key role in activating microglial functions directed against the influenza virus infection by inducing neuronal IFN-gamma in the brain parenchyma. (C) 2001 Academic Press.
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