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

Despite the gap in our knowledge about the pathway between virus inoculation and CCL2 induction, our data clearly support a model in which neurons are the primary source of this chemokine during the most acute phase of the host response. Notably, deletion of CCL2 from neurons recapitulates the effect of systemic deletion in mice treated with anti-CCL2 immunoglobulin ( Figure 6F compared to Figure 4D ) -the inflammatory monocyte infiltrate is reduced by about 70% in both conditions at 18-24 hpi. Presumably, the remaining infiltrate in both experiments is CCL7-dependent, although the cellular source of this other CCR2 ligand is currently unknown. These findings suggest an intriguing maladaptive response: neurons respond to brain inoculation with TMEV by producing copious amounts of a chemokine that serves to recruit the inflammatory monocytes into the brain that ultimately kill those same neurons [4] . While the current study does not address the impact of a curtailed monocyte response on viral clearance or eventual lymphocyte recruitment, anecdotal evidence indicates that CCR2 -/mice do not succumb to lethal infection and, indeed, do not show any apparent adverse effects at later timepoints (out to several months). Studies assessing the impact of CCR2 deletion on hippocampal neuropathology are ongoing.