title: A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection.
abstract: Polymorphisms in the essential autophagy gene Atg16L1 have been linked with susceptibility to Crohn's disease, a major type of inflammatory bowel disease (IBD). Although the inability to control intestinal bacteria is thought to underlie IBD, the role of Atg16L1 during extracellular intestinal bacterial infections has not been sufficiently examined and compared to the function of other IBD susceptibility genes, such as Nod2, which encodes a cytosolic bacterial sensor. We find that Atg16L1 mutant mice are resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. An Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, but this hyperimmune phenotype and its protective effects are lost in Atg16L1/Nod2 double-mutant mice. These results reveal an immunosuppressive function of Atg16L1 and suggest that gene variants affecting the autophagy pathway may have been evolutionarily maintained to protect against certain life-threatening infections.
authors: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors: Amanda M
authors: AM
authors: Marchiando
authors: Deepshika
authors: D
authors: Ramanan
authors: Yi
authors: Y
authors: Ding
authors: Luis E
authors: LE
authors: Gomez
authors: Vanessa M
authors: VM
authors: Hubbard-Lucey
authors: Katie
authors: K
authors: Maurer
authors: Caihong
authors: C
authors: Wang
authors: Joshua W
authors: JW
authors: Ziel
authors: Nico
authors: N
authors: van Rooijen
authors: Gabriel
authors: G
authors: Nuñez
authors: B Brett
authors: BB
authors: Finlay
authors: Indira U
authors: IU
authors: Mysorekar
authors: Ken
authors: K
authors: Cadwell
mesh_terms: D000818:Animals; D000071183:Autophagy-Related Proteins; D058491:Bacterial Load; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology*; D044082:Citrobacter rodentium / Q000276:immunology*; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins
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