The Crohn's disease: Associated ATG16L1 variant and Salmonella invasion

Jeannette S. Messer, Stephen F. Murphy, Mark F. Logsdon, James P. Lodolce, Wesley A. Grimm, Sarah J. Bartulis, Tiphanie P. Vogel, Melisa Burn, David L. Boone*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

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-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.

Original languageEnglish (US)
Article numbere002790
JournalBMJ open
Volume3
Issue number6
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Messer, J. S., Murphy, S. F., Logsdon, M. F., Lodolce, J. P., Grimm, W. A., Bartulis, S. J., Vogel, T. P., Burn, M., & Boone, D. L. (2013). The Crohn's disease: Associated ATG16L1 variant and Salmonella invasion. BMJ open, 3(6), [e002790]. https://doi.org/10.1136/bmjopen-2013-002790