Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response.
Nat Commun
; 10(1): 3273, 2019 07 22.
Article
in En
| MEDLINE
| ID: mdl-31332169
Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-ß (IFN-ß) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-ß response. The effect of acetate on RSV infection was abolished in Gpr43-/- mice. Our findings reveal antiviral effects of acetate involving IFN-ß in lung epithelial cells and engagement of GPR43 and IFNAR.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interferon Type I
/
Respiratory Syncytial Virus Infections
/
Receptors, G-Protein-Coupled
/
Microbiota
/
Acetates
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2019
Document type:
Article
Affiliation country:
Brasil
Country of publication:
Reino Unido