FIGURE 1.

The dual role of CCR2-expressing monocytes during West Nile virus (WNV) infection. The function of CCR2 on monocytes may involve two distinct steps: egress from the bone marrow induced early following WNV infection, and their migration into the WNV-infected central nervous system (CNS). However, the role of CCR2-expressing monocytes is highly dependent on the mode of infection utilized in mouse models. With peripheral infection (A), WNV induces a monocytosis within several days post infection. Genetic deficiency or pharmacological blockade of CCR2 in mice (red arrow) results in monocytopenia and leads to decreased monocyte infiltration into the CNS, enhanced viral titers in the brain and increased mortality. Therefore, CCR2-mediated monocytosis and the subsequent migration of monocytes into the inflamed CNS are protective (green arrows). In contrast using an intranasal infection model of WNV infection (B), the migration of CCR2-expressing monocytes into the CNS has also been shown to promote pathogenesis (red arrow) in mice. Thus, blocking CCR2 using anti-CCL2 antibodies in this model prolongs survival (green) in mice.