CCR2-mediated signals are dispensable for inflammatory monocyte trafficking into liver during Listeria monocytogenes infection (133.11)

Abstract Trafficking of leukocytes into peripheral tissues is essential for immune defense. Murine models demonstrate that Ly6Chigh inflammatory monocytes traffic to sites of infection and play a crucial role in innate immunity. The recruitment of inflammatory monocyte is dependent on CCR2, a chemokine receptor that responds to MCP-1 and MCP-3. CCR2-/- mice have decreased number of inflammatory monocytes in the periphery due to their inability to traffic out of the bone marrow. Retention of monocytes in the bone marrow markedly increases the susceptibility to Listeria monocytogenes infection. Although inflammatory monocytes circulating in the bloodstream continue expressing surface CCR2, it remains unclear whether CCR2 is required for monocyte trafficking into and within peripheral tissues. In this study, we investigated the trafficking of inflammatory monocytes to the liver, a major peripheral site of L. monocytogenes infection. By tracing inflammatory monocytes which were adoptively transferred into the bloodstream, we found that CCR2+/+ and CCR2-/- monocytes trafficked similarly into infected livers. Histological and intravital imaging showed that CCR2 was dispensable for monocyte migration within the liver. Our studies demonstrate that CCR2-mediated signals principally facilitate monocyte emigration from the bone marrow and are dispensable for tissue infiltration during bacterial infection.