EBioMedicine (Mar 2022)
Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis
- Krist H. Antunes,
- Renato T. Stein,
- Caroline Franceschina,
- Emanuelle F. da Silva,
- Deise N. de Freitas,
- Josiane Silveira,
- Magáli Mocellin,
- Lidiane Leitão,
- José L. Fachi,
- Laís P. Pral,
- Amanda Gonzalez,
- Sarah Oliveira,
- Leonardo Duarte,
- Gisele Cassão,
- João I.B. Gonçalves,
- Tatiane M. Reis,
- Bruno L Abbadi,
- Maiele Dornelles,
- Nathália D.M. Sperotto,
- Maurício Rigo,
- Hosana Rodrigues,
- Marcus Jones,
- Matias Epifanio,
- Suzana Guima,
- João C. Setubal,
- Taissa R. Jorge,
- Daniel S. Mansur,
- Fabiana Q. Mayer,
- Ana Paula M. Varela,
- Cristiano V. Bizarro,
- Pablo Machado,
- Luiz A. Basso,
- Fernando P. Polack,
- Adnan Custovic,
- Marco A.R. Vinolo,
- Ana Paula D. de Souza
Affiliations
- Krist H. Antunes
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Renato T. Stein
- Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil; Corresponding authors.
- Caroline Franceschina
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Emanuelle F. da Silva
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Deise N. de Freitas
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Josiane Silveira
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Magáli Mocellin
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Lidiane Leitão
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- José L. Fachi
- Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil
- Laís P. Pral
- Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil
- Amanda Gonzalez
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Sarah Oliveira
- Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil
- Leonardo Duarte
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Gisele Cassão
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- João I.B. Gonçalves
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Tatiane M. Reis
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Bruno L Abbadi
- Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
- Maiele Dornelles
- Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
- Nathália D.M. Sperotto
- Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
- Maurício Rigo
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Hosana Rodrigues
- Laboratory of Nutritional Genomics, School of Applied Sciences, University of Campinas, Limeira, São Paulo, Brazil
- Marcus Jones
- Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Matias Epifanio
- Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil
- Suzana Guima
- Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, São Paulo, Brazil
- João C. Setubal
- Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, São Paulo, Brazil
- Taissa R. Jorge
- Laboratory of Imunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
- Daniel S. Mansur
- Laboratory of Imunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
- Fabiana Q. Mayer
- Molecular Biology Laboratory, Veterinary Research Institute Desidério Finamor, Agricultural Diagnosis and Research Department, Secretariat of Agriculture, Livestock and Irrigation, Eldorado do Sul, Rio Grande do Sul, Brazil
- Ana Paula M. Varela
- Molecular Biology Laboratory, Veterinary Research Institute Desidério Finamor, Agricultural Diagnosis and Research Department, Secretariat of Agriculture, Livestock and Irrigation, Eldorado do Sul, Rio Grande do Sul, Brazil
- Cristiano V. Bizarro
- Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
- Pablo Machado
- Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
- Luiz A. Basso
- Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
- Fernando P. Polack
- Fundación Infant, Buenos Aires, Argentina
- Adnan Custovic
- National Heart and Lung Institute, Imperial College London, UK
- Marco A.R. Vinolo
- Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil; Corresponding authors.
- Ana Paula D. de Souza
- Laboratory of Clinical and Experimental Immunology, Health and Life Science School - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90610-000, Brazil; Corresponding authors.
- Journal volume & issue
-
Vol. 77
p. 103891
Abstract
Summary: Background: Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice against RSV A2 strain infection by increasing interferon-β production and expression of interferon-stimulated genes (ISGs). However, the role of SFCA in RSV infection using strains isolated from patients is unknown. Methods: We first used RSV clinical strains isolated from infants hospitalized with RSV bronchiolitis to investigate the effects of in vitro SCFA-acetate treatment of human pulmonary epithelial cells. We next examined whether SCFA-acetate treatment is beneficial in a mouse model of RSV infection using clinical isolates. We sought to investigate the relationship of gut microbiota and fecal acetate with disease severity among infants hospitalized with RSV bronchiolitis, and whether treating their respiratory epithelial cells with SCFA-acetate ex-vivo impacts viral load and ISG expression. We further treated epithelial cells from SARS-CoV-2 infected patients with SCFA-acetate. Findings: In vitro pre-treatment of A549 cells with SCFA-acetate reduced RSV infection with clinical isolates and increased the expression of RIG-I and ISG15. Animals treated with SCFA-acetate intranasally recovered significantly faster, with reduction in the RSV clinical isolates viral load, and increased lung expression of IFNB1 and the RIG-I. Experiments in RIG-I knockout A549 cells demonstrated that the protection relies on RIG-I presence. Gut microbial profile was associated with bronchiolitis severity and with acetate in stool. Increased SCFA-acetate levels were associated with increasing oxygen saturation at admission, and shorter duration of fever. Ex-vivo treatment of patients’ respiratory cells with SCFA-acetate reduced RSV load and increased expression of ISGs OAS1 and ISG15, and virus recognition receptors MAVS and RIG-I, but not IFNB1. These SCFA-acetate effects were not found on cells from SARS-CoV-2 infected patients. Interpretation: SCFA-acetate reduces the severity of RSV infection and RSV viral load through modulation of RIG-I expression. Funding: FAPERGS (FAPERGS/MS/CNPq/SESRS no. 03/2017 - PPSUS 17/2551-0001380-8 and COVID-19 20/2551-0000258-6); CNPq 312504/2017-9; CAPES) - Finance Code 001.
