Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state

Plasmacytoid dendritic cells (pDCs) detect viruses initiating antiviral IFN-I responses. The microbiota is known to shape immune responses, but whether it influences pDC homeostasis and/or function is poorly understood. By comparing pDCs in germ-free and specific pathogen-free mice, we found that the microbiota supports homeostatic trafficking by eliciting constitutive levels of the chemokine CCL2 that engages CCR2. Mononuclear phagocytes were required for tonic CCL2 levels. CCL2 was particularly important for trafficking of a CCR2(hi) subset of pDCs that produced proinflammatory cytokines and was prone to apoptosis. We further demonstrated that CCR2 was also essential for pDC migration during inflammation. Wildtype:Ccr2(−/−) mixed BM chimeras revealed that CCR2 promotes pDC migration in a cell-intrinsic fashion. Overall, we identify a novel role for the microbiota in shaping immunity, which includes induction of CCL2 at levels that control homeostatic trafficking of pDCs.