Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells.

DOI
Publisher DOI
PubMed ID
32380006
Abstract
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.
Date Issued
2020-05-28
Publication Type
Article
Subjects
Microbiota conventional dendritic cells peripheral tolerance plasmacytoid dendritic cells type I interferons
Language(s)
en
Author(s)
Schaupp, Laura
Muth, Sabine
Rogell, Leif
Kofoed-Branzk, Michael
Melchior, Felix
Lienenklaus, Stefan
Klein, Matthias
Guendel, Fabian
Hain, Tobias
Schütze, Kristian
Grundmann, Ulrike
Schmitt, Vanessa
Dorsch, Martina
Spanier, Julia
Larsen, Pia-Katharina
Schwanz, Thomas
Jäckel, Sven
Reinhardt, Christoph
Bopp, Tobias
Danckwardt, Sven
Mahnke, Karsten
Heinz, Gitta Anne
Mashreghi, Mir-Farzin
Durek, Pawel
Kalinke, Ulrich
Kretz, Oliver
Huber, Tobias B
Weiss, Siegfried
Wilhelm, Christoph
Schild, Hansjörg
Diefenbach, Andreas
Probst, Hans Christian
Additional Credits
Journal
Cell
Publisher
Cell Press
ISSN
0092-8674
Access(Rights)
restricted
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