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Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells
- Source :
- Cell, United States
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Summary Environmental signals shape host physiology and fitness. Microbiota-derived cues are required to program conventional dendritic cells (cDCs) during the steady state so that they can promptly respond and initiate adaptive immune responses when encountering pathogens. However, the molecular underpinnings of microbiota-guided instructive programs are not well understood. Here, we report that the indigenous microbiota controls constitutive production of type I interferons (IFN-I) by plasmacytoid DCs. Using genome-wide analysis of transcriptional and epigenetic regulomes of cDCs from germ-free and IFN-I receptor (IFNAR)-deficient mice, we found that tonic IFNAR signaling instructs a specific epigenomic and metabolic basal state that poises cDCs for future pathogen combat. However, such beneficial biological function comes with a trade-off. Instructed cDCs can prime T cell responses against harmless peripheral antigens when removing roadblocks of peripheral tolerance. Our data provide fresh insights into the evolutionary trade-offs that come with successful adaptation of vertebrates to their microbial environment.
- Subjects :
- Male
Receptor, Interferon alpha-beta
Adaptive Immunity
CD8-Positive T-Lymphocytes
Biology
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
Animals
Epigenetics
Receptor
030304 developmental biology
Epigenomics
0303 health sciences
Microbiota
Peripheral tolerance
Dendritic Cells
peripheral tolerance
Cell biology
Mice, Inbred C57BL
type I interferons
plasmacytoid dendritic cells
conventional dendritic cells
Interferon Type I
Female
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 181
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....492822246d126a29510f0e0a9bba9e23