Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection

Charles L Howe; Reghann G. LaFrance-Corey; Emma N Goddery; Kanish Mirchia

Serum (A), whole brain (B), and microdissected hippocampus (C) were collected at 0, 3, 6, 12, and 24 h following intracranial inoculation with TMEV. Absolute levels of CCL2 were measured by ELISA. Each dot represents an individual animal. The bar graph shows mean ± 95% confidence intervals from aggregate data. A minimum of 3 mice were used per tissue per timepoint and the hippocampal samples were collected in a separate experiment from the whole brain samples. All results were analyzed by one-way ANOVA. CCL2 was induced in serum, whole brain, and hippocampus (P<0.001 for each factor in each tissue compared to 0 hpi). Brain sections collected at 0 (D, G), 6 (E, H), and 24 hpi (F, I) were immunostained to reveal CCL2 expression. In the hippocampus there was weak, diffuse signal in uninfected mice (D, G) that increased markedly at 6 hpi (E, H). By 24 hpi the signal intensity had decreased and exhibited a more punctate pattern (F, I). Scale bar in I is 50 µm and refers to G-I. CA1 = Cornu Ammonis 1 formation; sr = stratum radiatum; slm = stratum lacunosum-moleculare. Immunostaining is representative of more than 3 mice per timepoint in more than 3 separate experiments.