Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant

Kuballa, Petric; Huett, Alan; Rioux, John D.; Daly, Mark J.; Xavier, Ramnik J.

Abstract

The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the pathogenesis of Crohn's disease. A single common coding variant in the autophagy protein ATG16L1 predisposes individuals to the development of Crohn's disease: while ATG16L1 encoding threonine at amino acid position 300 (ATG16L1*300T) confers protection, ATG16L1 encoding for alanine instead of threonine (ATG16L1*300A, also known as T300A) mediates risk towards the development of Crohn's disease. Here we report that, in human epithelial cells, the Crohn's disease-associated ATG16L1 coding variant shows impairment in the capture of internalized Salmonella within autophagosomes. Thus, we propose that the association of ATG16L1*300A with increased risk of Crohn's disease is due to impaired bacterial handling and lowered rates of bacterial capture by autophagy. © 2008 Kuballa et al.

Citation

Kuballa, P., Huett, A., Rioux, J. D., Daly, M. J., & Xavier, R. J. (2008). Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLoS ONE, 3(10), Article e3391. https://doi.org/10.1371/journal.pone.0003391

• Journal Article Type: Article
• Acceptance Date: Sep 18, 2008
• Online Publication Date: Oct 13, 2008
• Publication Date: Oct 13, 2008
• Deposit Date: Aug 15, 2022
• Publicly Available Date: Aug 15, 2022
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 10
• Article Number: e3391
• DOI: https://doi.org/10.1371/journal.pone.0003391
• Public URL: https://nottingham-repository.worktribe.com/output/3181833
• Publisher URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003391