Macrophage depletion in CCR2-/- mice delays bacterial clearance and enhances neutrophil infiltration in an acute otitis media model.

Otitis media (OM) is a common and potentially serious disease of childhood. While OM is multifactorial on origin, bacterial infection is a unifying component. Many studies have established a critical role for innate immunity in bacterial clearance and OM resolution. A key component of innate immunity is the recruitment of immune and inflammatory cells, including macrophages. To explore the role of macrophages in OM, we evaluated the expression of genes related to macrophage function during a complete episode of acute OM in the mouse caused by middle ear (ME) inoculation with Haemophilus influenzae. We also combined CCR2 deficiency with chlodronate liposome toxicity to deplete macrophages during OM. Macrophage genes were robustly regulated during OM. Moreover, macrophage depletion enhanced and prolonged the infiltration of neutrophils into the infected ME, and increased the persistence of bacterial infection. The results illustrate the critical role played by macrophages in OM resolution.