Chemokine receptor expression patterns delineate distinct interstitial macrophage subsets in the lung and define a trajectory from monocytes to mature macrophages, bulk RNA-sequencing data

Inflammatory chemokine receptors CCR1, CCR2 and CCR5 are critical for directing recruitment of monocytes and macrophages in the context of inflammation. However, the discrete role for each receptor in monocyte/macrophage biology remains poorly understood, with previous reports citing receptor redundancy. Here, we have used transcriptomic approaches to examine inflammatory chemokine receptor expression on lung interstitial macrophage populations. We have demonstrated that interstitial macrophages can be divided into three distinct subsets, each of which express specific patterns of chemokine receptors, and that there are dynamic changes in chemokine receptor expression as macrophages differentiate from monocytes in the lung. Furthermore, macrophages expressing different combinations of chemokine receptors are transcriptionally distinct from one another, suggesting non-redundant functions for CCR 1, 2 and 5. Finally, we examined changes in macrophage chemokine receptor expression in vitro after treatment with varied TLR ligands, and show that CCR1 is specifically increased in response to bacterial but not viral ligands. Our data provide compelling evidence that macrophage chemokine receptor expression is not redundant, but specific and maleable in response to discrete inflammatory stimuli.