Acetate coordinates neutrophil and ILC3 responses against <i>C. difficile</i> through FFAR2
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- José Luís Fachi
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
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- Cristiane Sécca
- Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 2
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- Patrícia Brito Rodrigues
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
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- Felipe Cézar Pinheiro de Mato
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
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- Blanda Di Luccia
- Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 2
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- Jaqueline de Souza Felipe
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
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- Laís Passariello Pral
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
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- Marcella Rungue
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil 3
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- Victor de Melo Rocha
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil 3
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- Fabio Takeo Sato
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
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- Ulliana Sampaio
- Department of Food Technology, School of Food Engineering, University of Campinas, Campinas, Brazil 4
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- Maria Teresa Pedrosa Silva Clerici
- Department of Food Technology, School of Food Engineering, University of Campinas, Campinas, Brazil 4
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- Hosana Gomes Rodrigues
- Laboratory of Nutrients & Tissue Repair, School of Applied Sciences, University of Campinas, Limeira, Brazil 5
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- Niels Olsen Saraiva Câmara
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil 6
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- Sílvio Roberto Consonni
- Department of Biochemistry & Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil 7
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- Angélica Thomaz Vieira
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil 3
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- Sergio Costa Oliveira
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil 3
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- Charles Reay Mackay
- Department of Immunology, Monash University, Melbourne, Australia 8
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- Brian T. Layden
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 9
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- Karina Ramalho Bortoluci
- Center for Cellular and Molecular Therapy, Federal University of São Paulo, Vl Clementino, São Paulo, Brazil 11
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- Marco Colonna
- Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 2
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- Marco Aurélio Ramirez Vinolo
- Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil 1
抄録
<jats:p>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.</jats:p>
収録刊行物
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- Journal of Experimental Medicine
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Journal of Experimental Medicine 217 (3), 2019-12-26
Rockefeller University Press