Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state.
Plasmacytoid dendritic cells (pDCs) detect viruses initiating antiviral type I interferon 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 CCR2hisubset of pDCs that produced proinflammatory cytokines and was prone to apoptosis. We further demonstrated that CCR2 was also essential for pDC migration during inflammation. Wild-type (WT):Ccr2-/-mixed bone marrow chimeras revealed that CCR2 promotes pDC migration in a cell-intrinsic manner. Overall, we identify a novel role for the microbiota in shaping immunity, which includes induction of CCL2 levels that control homeostatic trafficking of pDCs.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.|Janssen Research and Development LLC, Spring House, Pennsylvania, USA.
M
M
Swiecki
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
H L
HL
Miller
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
R
R
Sesti-Costa
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
M
M
Cella
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
S
S
Gilfillan
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
M
M
Colonna
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D012157:Mononuclear Phagocyte System; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D054390:Receptors, CCR2