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Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis.
Antunes, Krist H; Stein, Renato T; Franceschina, Caroline; da Silva, Emanuelle F; de Freitas, Deise N; Silveira, Josiane; Mocellin, Magáli; Leitão, Lidiane; Fachi, José L; Pral, Laís P; Gonzalez, Amanda; Oliveira, Sarah; Duarte, Leonardo; Cassão, Gisele; Gonçalves, João I B; Reis, Tatiane M; Abbadi, Bruno L; Dornelles, Maiele; Sperotto, Nathália D M; Rigo, Maurício; Rodrigues, Hosana; Jones, Marcus; Epifanio, Matias; Guima, Suzana; Setubal, João C; Jorge, Taissa R; Mansur, Daniel S; Mayer, Fabiana Q; Varela, Ana Paula M; Bizarro, Cristiano V; Machado, Pablo; Basso, Luiz A; Polack, Fernando P; Custovic, Adnan; Vinolo, Marco A R; de Souza, Ana Paula D.
  • Antunes KH; 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.
  • Stein RT; Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil. Electronic address: rstein@pucrs.br.
  • Franceschina C; 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.
  • da Silva EF; 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.
  • de Freitas DN; 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.
  • Silveira J; 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.
  • Mocellin M; 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.
  • Leitão L; 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.
  • Fachi JL; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
  • Pral LP; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
  • Gonzalez A; 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.
  • Oliveira S; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
  • Duarte L; 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.
  • Cassão G; 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.
  • Gonçalves JIB; 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.
  • Reis TM; 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.
  • Abbadi BL; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Dornelles M; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Sperotto NDM; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Rigo M; 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.
  • Rodrigues H; Laboratory of Nutritional Genomics, School of Applied Sciences, University of Campinas, Limeira, São Paulo, Brazil.
  • Jones M; Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil.
  • Epifanio M; Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil.
  • Guima S; Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, São Paulo, Brazil.
  • Setubal JC; Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, São Paulo, Brazil.
  • Jorge TR; Laboratory of Imunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
  • Mansur DS; Laboratory of Imunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
  • Mayer FQ; 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.
  • Varela APM; 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.
  • Bizarro CV; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Machado P; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Basso LA; Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Polack FP; Fundación Infant, Buenos Aires, Argentina.
  • Custovic A; National Heart and Lung Institute, Imperial College London, UK.
  • Vinolo MAR; Department of Pediatrics, School of Medicine, PUCRS, São Lucas Hospital PUCRS, Porto Alegre, Rio Grande do Sul 90610-000, Brazil. Electronic address: mvinolo@g.unicamp.br.
  • de Souza APD; 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. Electronic address: ana.duarte@pucrs.br.
EBioMedicine ; 77: 103891, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1709186
ABSTRACT

BACKGROUND:

Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice against RSV A2 strain infection by increasing interferon-ß 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bronchiolitis / Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections / COVID-19 Type of study: Prognostic study Limits: Animals / Humans / Infant Language: English Journal: EBioMedicine Year: 2022 Document Type: Article Affiliation country: J.ebiom.2022.103891

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bronchiolitis / Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections / COVID-19 Type of study: Prognostic study Limits: Animals / Humans / Infant Language: English Journal: EBioMedicine Year: 2022 Document Type: Article Affiliation country: J.ebiom.2022.103891