GSE49109
Transcriptional profile in the colon in response to C. rodentium infection.
The identification of Atg16L1 as a susceptibility gene has implicated antibacterial autophagy in the pathogenesis of Crohn''s disease, a major type of inflammatory bowel disease (IBD). However, the role of Atg16L1 during extracellular bacterial infections of the intestine has not been sufficiently examined and compared to the function of other IBD susceptibility genes such as Nod2. We now find that Atg16L1 mutant mice are extraordinarily resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. We further demonstrate that Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, and that Atg16L1/Nod2 double mutant mice lose this advantage. These results reveal an unappreciated immuno-suppressive function of an IBD gene, and raise the possibility that gene variants that affect the autophagy pathway were evolutionarily maintained to protect against certain life-threatening infections. Overall design: Twenty samples have been analyzed. All are colonic tissue from mice. Controls are uninfected WT mice, uninfected Atg16L1 mutant mice (Atg16L1HM)  (n=3/genotype). Treatment conditions are tissue from WT and Atg16L1 mutant mice 6 days after C. rodentium infection (n=4/genotype) and 15 days after infection (n=3/genotype).