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

To determine the role of the CCL2:CCR2 axis in controlling inflammatory monocyte trafficking to the brain during acute TMEV infection, we quantified leukocyte infiltration in CCR2 knockout mice at 18 hpi (Figure 3) . We have previously established that our methods isolate three clearly distinguished populations that respond to TMEV infection: CD45 hi CD11b + Gr1 ++ 1A8inflammatory monocytes, CD45 hi CD11b ++ Gr1 + 1A8 + neutrophils, and CD45 mid CD11b mid Gr1 -1A8microglia [4]. In wildtype mice at 18 hpi we observed robust populations of all three cell types ( Figure 3A , 3C), with inflammatory monocytes making up about 25% of the total CD45 + population ( Figure 3E ). In the absence of CCR2 expression there was marked suppression of inflammatory monocyte infiltration and a relative increase in neutrophil recruitment, with no change in microglia ( Figure 3B, 3D) . Indeed, inflammatory monocytes were reduced to less than 3% of total CD45 + cells (WT vs CCR2ko: P=0.0004 by Dunnett's method; Figure 3E ). We conclude that the CCR2 receptor axis is the primary driver for inflammatory monocyte infiltration during acute TMEV infection.