TY - JOUR
T1 - A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection
AU - Marchiando, Amanda M.
AU - Ramanan, Deepshika
AU - Ding, Yi
AU - Gomez, Luis E.
AU - Hubbard-Lucey, Vanessa M.
AU - Maurer, Katie
AU - Wang, Caihong
AU - Ziel, Joshua W.
AU - Van Rooijen, Nico
AU - Nuñez, Gabriel
AU - Finlay, B. Brett
AU - Mysorekar, Indira U.
AU - Cadwell, Ken
N1 - Funding Information:
We would like to thank Joel Ernst, Gretchen Diehl, Yi Yang, Dan Littman, Davida Smyth, and Andrew Darwin for providing advice and reagents; Jiri Zavidil and Elisa Venturini of the NYU Genome Technology Center for deep sequencing; and Stuart Brown and Zuojian Tang of NYU Center for Health Informatics and Bioinformatics for data analysis. This research was supported by NIH grants R01 DK093668 (A.M., L.E.G., K.C.), R01 DK61707 (G.N.), T32 AI007647 (A.M. and V.M.H.), K99/R00 DK080643 (I.U.M.), P30 DK052574 (I.U.M. and C.W.), F32 HL115974 (V.M.H.), and T32 AI100853 (K.M.); the Crohn’s & Colitis Foundation of America (K.C.); and the Dale F. Frey Award from the Damon Runyon Cancer Research Foundation (K.C.). The NYU IHC Core is supported in part by the NYUCI center support grant P30 CA16087.
PY - 2013/8/14
Y1 - 2013/8/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84882369710&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2013.07.013
DO - 10.1016/j.chom.2013.07.013
M3 - Article
C2 - 23954160
AN - SCOPUS:84882369710
SN - 1931-3128
VL - 14
SP - 216
EP - 224
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -