Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2.
J Exp Med
; 217(3)2020 03 02.
Article
in En
| MEDLINE
| ID: mdl-31876919
Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infections (CDIs), which cause intestinal disease ranging from mild diarrhea to pseudomembranous colitis. Here, we examined the impact of a microbiota-derived metabolite, short-chain fatty acid acetate, on an acute mouse model of CDI. We found that administration of acetate is remarkably beneficial in ameliorating disease. Mechanistically, we show that acetate enhances innate immune responses by acting on both neutrophils and ILC3s through its cognate receptor free fatty acid receptor 2 (FFAR2). In neutrophils, acetate-FFAR2 signaling accelerates their recruitment to the inflammatory sites, facilitates inflammasome activation, and promotes the release of IL-1ß; in ILC3s, acetate-FFAR2 augments expression of the IL-1 receptor, which boosts IL-22 secretion in response to IL-1ß. We conclude that microbiota-derived acetate promotes host innate responses to C. difficile through coordinate action on neutrophils and ILC3s.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Enterocolitis, Pseudomembranous
/
Clostridioides difficile
/
Clostridium Infections
/
Receptors, G-Protein-Coupled
/
Immunity, Innate
/
Acetates
/
Neutrophils
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2020
Document type:
Article
Affiliation country:
Brasil
Country of publication:
Estados Unidos