Induction of diabetes in the RIP-B7.1 mouse model is critically dependent on TLR3 and MyD88 pathways and is associated with alterations in the intestinal microbiome.
Diabetes
; 63(2): 619-31, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24353176
RIP-B7.1 transgenic mice express B7.1 costimulatory molecules in pancreatic islets and develop diabetes after treatment with polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA and agonist of Toll-like receptor (TLR) 3 and retinoic acid-inducible protein I. We used this model to investigate the role of TLR pathways and intestinal microbiota in disease progression. RIP-B7.1 mice homozygous for targeted disruption of TLR9, TLR3, and myeloid differentiation factor-88 (MyD88), and most of the wild-type RIP-B7.1 mice housed under normal conditions remained diabetes-free after poly I:C administration. However, the majority of TLR9-deficient mice and wild-type animals treated with poly I:C and an antibiotic developed disease. In sharp contrast, TLR3- and MyD88-deficient mice were protected from diabetes following the same treatment regimen. High-throughput DNA sequencing demonstrated that TLR9-deficient mice treated with antibiotics plus poly I:C had higher bacterial diversity compared with disease-resistant mice. Furthermore, principal component analysis suggested that TLR9-deficient mice had distinct gut microbiome compared with the diabetes-resistant mice. Finally, the administration of sulfatrim plus poly I:C to TLR9-deficient mice resulted in alterations in the abundance of gut bacterial communities at the phylum and genus levels. These data imply that the induction of diabetes in the RIP-B7.1 model is critically dependent on TLR3 and MyD88 pathways, and involves modulation of the intestinal microbiota.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Diabetes Mellitus
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Receptor 3 Toll-Like
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Fator 88 de Diferenciação Mieloide
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Intestinos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2014
Tipo de documento:
Article
País de publicação:
Estados Unidos