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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Marchiando AM,Ramanan D,Ding Y,Gomez LE,Hubbard-Lucey VM,Maurer K,Wang C,Ziel JW,van Rooijen N,Nuñez G,Finlay BB,Mysorekar IU,Cadwell K

doi

10.1016/j.chom.2013.07.013

subject

Has Abstract

pub_date

2013-08-14 00:00:00

pages

216-24

issue

2

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(13)00261-8

journal_volume

14

pub_type

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