The chemokine CCL5 induces selective migration of bovine classical monocytes and drives their differentiation into LPS-hyporesponsive macrophages in vitro

Human and mouse studies indicate distinct roles of selected chemokines for monocyte subset attraction. We therefore analyzed the still unknown sensitivity and response of bovine monocyte subsets toward two monocyte-attracting chemokines (CCL2, CCL5). Only CCL5 induced a significant Ca2+influx and migration response in bovine monocytes, with classical and intermediate monocytes being significantly stimulated and attracted compared to nonclassical monocytes. The presence of CCL5 during in vitro macrophage differentiation did not alter their capacity to phagocytize or to generate reactive oxygen species upon stimulation with E. coli. However, macrophages differentiated in the presence of CCL5 displayed an altered phenotype with significantly less expressed CD14 and MHC class II molecules, whereas CD16 was upregulated. Moreover, CCL5-differentiated macrophages displayed a reduced upregulation of CXCL8, ARG1, IL6 and IL10 mRNA. Taken together, CCL5 but not CCL2 mainly attract bovine classical monocytes and promote their differentiation into LPS-hypo-responsive macrophages.