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Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2017 Jul; Vol. 10 (4), pp. 936-945. Date of Electronic Publication: 2016 Nov 09. - Publication Year :
- 2017
-
Abstract
- 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 CCR2 <superscript>hi</superscript> 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. Wild-type (WT):Ccr2 <superscript>-/-</superscript> 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.
- Subjects :
- Animals
Apoptosis
Cells, Cultured
Cytokines metabolism
Homeostasis
Inflammation microbiology
Inflammation Mediators metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mononuclear Phagocyte System
Receptors, CCR2 genetics
Receptors, CCR2 metabolism
Specific Pathogen-Free Organisms
Cell Movement
Chemokine CCL2 metabolism
Dendritic Cells immunology
Inflammation immunology
Microbiota immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 27827374
- Full Text :
- https://doi.org/10.1038/mi.2016.99