A specific gene-microbe interaction drives the development of Crohn's disease-like colitis in mice.
Sci Immunol
; 4(34)2019 04 19.
Article
de En
| MEDLINE
| ID: mdl-31004013
ABSTRACT
Bacterial dysbiosis is associated with Crohn's disease (CD), a chronic intestinal inflammatory disorder thought to result from an abnormal immune response against intestinal bacteria in genetically susceptible individuals. However, it is unclear whether dysbiosis is a cause or consequence of intestinal inflammation and whether overall dysbiosis or specific bacteria trigger the disease. Here, we show that the combined deficiency of NOD2 and phagocyte NADPH oxidase, two CD susceptibility genes, triggers early-onset spontaneous TH1-type intestinal inflammation in mice with the pathological hallmarks of CD. Disease was induced by Mucispirillum schaedleri, a Gram-negative mucus-dwelling anaerobe. NOD2 and CYBB deficiencies led to marked accumulation of Mucispirillum, which was associated with impaired neutrophil recruitment and killing of the bacterium by luminal neutrophils. Maternal immunoglobulins against Mucispirillum protected mutant mice from disease during breastfeeding. Our results indicate that a specific intestinal microbe triggers CD-like disease in the presence of impaired clearance of the bacterium by innate immunity.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Bactéries
/
Maladie de Crohn
/
Dysbiose
/
Interactions hôte-microbes
/
Muqueuse intestinale
Limites:
Animals
Langue:
En
Journal:
Sci Immunol
Année:
2019
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique