The Crohn's disease: associated ATG16L1 variant and Salmonella invasion.
BMJ Open
; 3(6)2013 Jun 20.
Article
en En
| MEDLINE
| ID: mdl-23794574
ABSTRACT
OBJECTIVE:
A common genetic coding variant in the core autophagy gene ATG16L1 is associated with increased susceptibility to Crohn's disease (CD). The variant encodes an amino acid change in ATG16L1 such that the threonine at position 300 is substituted with an alanine (ATG16L1 T300A). How this variant contributes to increased risk of CD is not known, but studies with transfected cell lines and gene-targeted mice have demonstrated that ATG16L1 is required for autophagy, control of interleukin-1-ß and autophagic clearance of intracellular microbes. In addition, studies with human cells expressing ATG16L1 T300A indicate that this variant reduces the autophagic clearance of intracellular microbes. DESIGN/RESULTS:
We demonstrate, using somatically gene-targeted human cells that the ATG16L1 T300A variant confers protection from cellular invasion by Salmonella. In addition, we show that ATG16L1-deficient cells are resistant to bacterial invasion.CONCLUSIONS:
These results suggest that cellular expression of ATG16L1 facilitates bacterial invasion and that the CD-associated ATG16L1 T300A variant may confer protection from bacterial infection.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
BMJ Open
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos