Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response

Autor(es):Mostrar menos -

Antunes, Krist Helen ^[1] ; Fachi, Jose Luis ^[2] ; de Paula, Rosemeire ^[2] ; da Silva, Emanuelle Fraga ^[1] ; Pral, Lais Passariello ^[2] ; dos Santos, Adara Aurea ^[3] ; Malaquias Dias, Greicy Brisa ^[3] ; Vargas, Jose Eduardo ^[4] ; Puga, Renato ^[5] ; Mayer, Fabiana Quoos ^[6] ; Maito, Fabio ^[7] ; Zarate-Blades, Carlos R. ^[8] ; Ajami, Nadim J. ^[9] ; St Ana, Marcella Ramos ^[10] ; Candreva, Thamiris ^[11] ; Rodrigues, Hosana Gomes ^[11] ; Schmiele, Marcio ^[12] ; Pedrosa Silva Clerici, Maria Teresa ^[13] ; Proenca-Modena, Jose Luiz ^[14] ; Vieira, Angelica Thomas ^[15] ; Mackay, Charles R. ^[16] ; Mansur, Daniel ^[3] ; Caballero, Mauricio T. ^[17] ; Marzec, Jacqui ^[18] ; Li, Jianying ^[18] ; Wang, Xuting ^[18] ; Bell, Douglas ^[18] ; Polack, Fernando P. ^{[17, 19]} ; Kleeberger, Steven R. ^[18] ; Stein, Renato T. ^[20] ; Ramirez Vinolo, Marco Aurelio ^[2] ; Duarte de Souza, Ana Paula ^{[1, 21]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Pontificia Univ Catolica Rio Grande do Sul, Sch Med, Lab Clin & Expt Immunol, Infant Ctr, BR-90610000 Porto Alegre, RS - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Immunoinflammat, BR-13083007 Campinas, SP - Brazil

^[3] Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Microbiol Immunol & Parasitol, Lab Imunobiol, BR-88040900 Florianopolis, SC - Brazil

^[4] Univ Passo Fundo, Biol Sci Inst ICB, BR-99052900 Passo Fundo, RS - Brazil

^[5] HIAE, Clin Res Ctr, BR-05652900 Sao Paulo - Brazil

^[6] Secretariat Agr Livestock & Irrigat, Agr Diag & Res Dept, Vet Res Inst Desiderio Finamor, Mol Biol Lab, BR-92990000 Eldorado Do Sul, RS - Brazil

^[7] Pontificia Univ Catolica Rio Grande do Sul, Hlth Sci Sch, Lab Pathol, BR-90610000 Porto Alegre, RS - Brazil

^[8] Univ Fed Santa Catarina, UFSC, Dept Microbiol Immunol & Parasitol, Lab Limmunoregulat, BR-8804900 Florianopolis, SC - Brazil

^[9] Baylor Coll Med, Dept Mol Virol & Microbiol, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 - USA

^[10] Univ Estadual Campinas, Sch Appl Sci, Lab Nutr Genom, BR-13484350 Limeira, SP - Brazil

^[11] Univ Estadual Campinas, Sch Appl Sci, Lab Nutrients & Tissue Repair, BR-13484350 Limeira, SP - Brazil

^[12] Fed Univ Jequitinhonha & Mucuri Valleys UFVJM, Inst Sci & Technol, BR-39803371 Teofilo Otoni, MG - Brazil

^[13] Univ Estadual Campinas, UNICAMP, Sch Food Engn, Dept Food Technol, Monteiro Lobato 80, BR-13083970 Campinas, SP - Brazil

^[14] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Emerging Viruses Study Lab, BR-13083970 Campinas, SP - Brazil

^[15] Univ Fed Minas Gerais, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG - Brazil

^[16] Monash Univ, Biodiscovery Res Inst, Clayton, Vic 3800 - Australia

^[17] Fdn INFANT, RA-1406 Buenos Aires, DF - Argentina

^[18] NIEHS, NIH, Durham, NC 27709 - USA

^[19] Vanderbilt Univ, EUA, Nashville, TN 37240 - USA

^[20] Sao Lucas Hosp PUCRS, Dept Pediat, Sch Med, Infant Ctr, BR-90610000 Porto Alegre, RS - Brazil

^[21] Pontificia Univ Catolica Rio Grande do Sul, Sch Heath Sci, BR-90610000 Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 10, JUL 22 2019.
• Citações Web of Science: 1

Resumo

Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-beta (IFN-beta) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-beta response. The effect of acetate on RSV infection was abolished in Gpr43(-/-) mice. Our findings reveal antiviral effects of acetate involving IFN-beta in lung epithelial cells and engagement of GPR43 and IFNAR. (AU)

• Processo FAPESP: 13/06810-4 - Mecanismos de ação dos ácidos graxos ômega-3 e ômega-6 no processo de reparo tecidual: enfoque neuro-imunológico
• Beneficiário: Hosana Gomes Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/06577-9 - Mecanismos envolvidos no efeito protetor dos ácidos graxos de cadeia curta frente à colite associada ao Clostridium difficile
• Beneficiário: José Luís Fachi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/10653-9 - Envolvimento dos ácidos graxos de cadeia curta e seu receptor (GPR43) na resposta imune a bactérias anaeróbias in vivo e in vitro
• Beneficiário: Marco Aurélio Ramirez Vinolo
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores