ATG16L1 deficiency in macrophages drives clearance of uropathogenic E. coli in an IL-1β-dependent manner
| Autor: | Joel D. Schilling, Jane W. Symington, N Owusu-Boaitey, Caihong Wang, Joy Twentyman, G Núñez, Indira U. Mysorekar, Reto A. Schwendener |
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| Přispěvatelé: | University of Zurich, Mysorekar, I U |
| Rok vydání: | 2015 |
| Předmět: |
Male
Interleukin-1beta caspase-1 Autophagy-Related Proteins urologic and male genital diseases Polymerase Chain Reaction Mice 0302 clinical medicine Uropathogenic Escherichia coli Immunology and Allergy bladder ATG16L1 Escherichia coli Infections Mice Knockout 0303 health sciences medicine.diagnostic_test 10061 Institute of Molecular Cancer Research Inflammasome Flow Cytometry Phenotype female genital diseases and pregnancy complications 3. Good health Blot 030220 oncology & carcinogenesis Urinary Tract Infections lysosome 2723 Immunology and Allergy Female medicine.drug autophagy Blotting Western Immunology Enzyme-Linked Immunosorbent Assay 610 Medicine & health Biology Article Microbiology Flow cytometry 03 medical and health sciences NLRP3 inflammasome In vivo medicine Animals Secretion 030304 developmental biology 2403 Immunology Macrophages Autophagy bacterial infections and mycoses Mice Inbred C57BL Disease Models Animal 570 Life sciences biology Carrier Proteins |
| Zdroj: | Mucosal immunology |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2015.7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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