Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2
| Autor: | Karina R. Bortoluci, Sílvio Roberto Consonni, Marcella Rungue, Charles R. Mackay, Jaqueline de Souza Felipe, Brian T. Layden, Cristiane Sécca, Niels Olsen Saraiva Câmara, Laís Passariello Pral, Fabio Takeo Sato, Hosana G. Rodrigues, Ulliana Marques Sampaio, José Luís Fachi, Marco Colonna, Victor de Melo Rocha, Blanda Di Luccia, Patrícia Brito Rodrigues, Maria Teresa Pedrosa Silva Clerici, Angélica T. Vieira, Felipe Cezar Pinheiro de Mato, Marco Aurélio Ramirez Vinolo, Sergio C. Oliveira |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Inflammasomes Neutrophils Immunology Acetates Article Receptors G-Protein-Coupled Microbiology Interleukin 22 Mice 03 medical and health sciences 0302 clinical medicine Immunity Free fatty acid receptor 2 medicine Animals Immunology and Allergy Receptor Research Articles Enterocolitis Pseudomembranous Innate immune system Clostridioides difficile Chemistry Inflammasome Pseudomembranous colitis medicine.disease Immunity Innate Mice Inbred C57BL 030104 developmental biology MODELOS ANIMAIS Clostridium Infections Dysbiosis Signal Transduction 030215 immunology medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP The Journal of Experimental Medicine |
| Popis: | Microbiota-derived acetate coordinates innate immune responses during intestinal Clostridium difficile infection through its cognate receptor FFAR2. Acetate accelerates early neutrophil recruitment and increases ILC3 expression of the IL-1 receptor, boosting ILC3 production of IL-22 in response to neutrophil-derived IL-1β. 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-1β; in ILC3s, acetate-FFAR2 augments expression of the IL-1 receptor, which boosts IL-22 secretion in response to IL-1β. We conclude that microbiota-derived acetate promotes host innate responses to C. difficile through coordinate action on neutrophils and ILC3s. Graphical Abstract |
| Databáze: | OpenAIRE |
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