Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota.
Animals
Bacteria
/ metabolism
Chromosomes, Bacterial
/ genetics
Diet, High-Fat
Endogenous Retroviruses
/ physiology
Homeostasis
Inflammation
/ immunology
Interferon Type I
/ metabolism
Keratinocytes
/ metabolism
Membrane Proteins
/ metabolism
Mice, Inbred C57BL
Microbiota
Nucleotidyltransferases
/ metabolism
Retroelements
/ genetics
Signal Transduction
Skin
/ immunology
T-Lymphocytes
/ immunology
Transcription, Genetic
STING
Staphylococcus epidermidis
T cells
antiretroviral
endogenous retrovirus
high fat diet
keratinocytes
microbiota
skin immunity
tissue repair
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
08 07 2021
08 07 2021
Historique:
received:
24
09
2020
revised:
10
04
2021
accepted:
14
05
2021
pubmed:
25
6
2021
medline:
4
1
2022
entrez:
24
6
2021
Statut:
ppublish
Résumé
The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratinocyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the microbiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for heightened ERV- expression in response to commensal colonization, leading to increased immune responses and tissue inflammation. Together, our results support the idea that the host may have co-opted its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-kingdom dialog that controls both tissue homeostasis and inflammation.
Identifiants
pubmed: 34166614
pii: S0092-8674(21)00650-4
doi: 10.1016/j.cell.2021.05.020
pmc: PMC8381240
pii:
doi:
Substances chimiques
Interferon Type I
0
Membrane Proteins
0
Retroelements
0
Sting1 protein, mouse
0
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, mouse
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3794-3811.e19Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102898/B/13/Z
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests Y.B. is a member of the advisory board of the journal Cell.
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