The Crohn's disease: associated ATG16L1 variant and Salmonella invasion
| Autor: | Sarah Bartulis, Jeannette S. Messer, Stephen F. Murphy, Tiphanie P. Vogel, Mark F Logsdon, Melisa Burn, David L. Boone, James P. Lodolce, Wesley A Grimm |
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| Rok vydání: | 2013 |
| Předmět: |
Salmonella
Gastroenterology and Hepatology medicine.disease_cause Microbiology 03 medical and health sciences 0302 clinical medicine Medicine Threonine Gene ATG16L1 030304 developmental biology 0303 health sciences business.industry Research Autophagy Correction General Medicine Transfection 3. Good health Cell culture 030220 oncology & carcinogenesis Immunology business Intracellular |
| Zdroj: | BMJ Open |
| ISSN: | 2044-6055 |
| Popis: | Objective A common genetic coding variant in the core autophagy gene ATG16L1 is associated with increased susceptibility to Crohn9s 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-β 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. |
| Databáze: | OpenAIRE |
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