Commensal viruses maintain intestinal intraepithelial lymphocytes via noncanonical RIG-I signaling.
Nat Immunol
; 20(12): 1681-1691, 2019 12.
Article
in En
| MEDLINE
| ID: mdl-31636462
ABSTRACT
Much attention has focused on commensal bacteria in health and disease, but the role of commensal viruses is understudied. Although metagenomic analysis shows that the intestine of healthy humans and animals harbors various commensal viruses and the dysbiosis of these viruses can be associated with inflammatory diseases, there is still a lack of causal data and underlying mechanisms to understand the physiological role of commensal viruses in intestinal homeostasis. In the present study, we show that commensal viruses are essential for the homeostasis of intestinal intraepithelial lymphocytes (IELs). Mechanistically, the cytosolic viral RNA-sensing receptor RIG-I in antigen-presenting cells can recognize commensal viruses and maintain IELs via a type I interferon-independent, but MAVS-IRF1-IL-15 axis-dependent, manner. The recovery of IELs by interleukin-15 administration reverses the susceptibility of commensal virus-depleted mice to dextran sulfate sodium-induced colitis. Collectively, our results indicate that commensal viruses maintain the IELs and consequently sustain intestinal homeostasis via noncanonical RIG-I signaling.
Full text:
1
Database:
MEDLINE
Main subject:
Colitis
/
Caliciviridae Infections
/
Norovirus
/
DEAD Box Protein 58
/
Intraepithelial Lymphocytes
/
Intestines
/
Antigen-Presenting Cells
Limits:
Animals
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2019
Type:
Article
Affiliation country:
China