ACKR2 aids the regulation of bone marrow eosinophils to promote monocyte differentiation and anti-bacterial immunity.

Chemokine receptors control cell migration within the body. Here we reveal interactions between eosinophils and monocytes in the bone marrow, indirectly controlled by the atypical chemokine receptor ACKR2. In the absence of ACKR2, there are decreased numbers of eosinophils in the bone marrow. As a result, eosinophil and monocyte interactions are reduced within the bone marrow niche, and are associated with changes in monocyte gene expression. Monocytes from ACKR2-/- mice are recruited to the tissues but are fundamentally altered in their ability to differentiate into macrophages, in the lung, peritoneal cavity and cavity wall. Bacterial elimination is impaired in ACKR2-/- mice during peritoneal infection. ACKR2 is therefore a key regulator of eosinophil-driven monocyte education in the bone marrow, required for full monocyte differentiation and macrophage function within the tissues.