title: ATG16L1 deficiency in macrophages drives clearance of uropathogenic E. coli in an IL-1β-dependent manner.
abstract: Urinary tract infections (UTIs) are frequent, commonly recurrent, and costly. Deficiency in a key autophagy protein, ATG16L1, protects mice from infection with the predominant bacterial cause of UTIs, Uropathogenic E. coli (UPEC). Here, we report that loss of ATG16L1 in macrophages accounts for this protective phenotype. Compared with wild-type macrophages, macrophages deficient in ATG16L1 exhibit increased uptake of UPEC and enhanced secretion of interleukin-1β (IL-1β). The increased IL-1β production is dependent upon activation of the NLRP3 inflammasome and caspase-1. IL-1β secretion was also enhanced during UPEC infection of ATG16L1-deficient mice in vivo, and inhibition of IL-1β signaling abrogates the ATG16L1-dependent protection from UTIs. Our results argue that ATG16L1 normally suppresses a host-protective IL-1β response to UPEC by macrophages.
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: J W
authors: JW
authors: Symington
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: C
authors: C
authors: Wang
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: J
authors: J
authors: Twentyman
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: N
authors: N
authors: Owusu-Boaitey
authors: Laboratory of Liposome Research, Institute of Molecular Cancer Research, Zurich, Switzerland.
authors: R
authors: R
authors: Schwendener
authors: Department of Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
authors: G
authors: G
authors: Núñez
authors: Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: J D
authors: JD
authors: Schilling
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: I U
authors: IU
authors: Mysorekar
mesh_terms: D000818:Animals; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D053583:Interleukin-1beta / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D014552:Urinary Tract Infections / Q000276:immunology*; D056689:Uropathogenic Escherichia coli / Q000276:immunology
chemical_list: C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C587672:IL1B protein, mouse; D053583:Interleukin-1beta