ATG16L1 deficiency in macrophages drives clearance of uropathogenic E. coli in an IL-1β-dependent manner.
ATG16L1 deficiency in macrophages drives clearance of uropathogenic E. coli in an IL-1β-dependent manner.
复制标题
巨噬细胞中ATG16L1缺乏以IL-1β依赖性方式驱动肝癌大肠杆菌清除。
DOI：
10.1038/mi.2015.7
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发表时间：
2015-11
影响因子：
8
通讯作者：
Mysorekar IU
中科院分区：
文献类型：
--
作者：
Symington JW;Wang C;Twentyman J;Owusu-Boaitey N;Schwendener R;Núñez G;Schilling JD;Mysorekar IU
尿路感染（UTI）是常见的，通常反复发作，费用昂贵。一种关键的自噬蛋白ATG 16 L1的缺乏可以保护小鼠免受尿路感染的主要细菌病原体，尿路致病性大肠杆菌的感染。大肠杆菌（UPEC）。在这里，我们报告了巨噬细胞中ATG 16 L1的丢失导致了这种保护性表型。与野生型巨噬细胞相比，缺乏ATG 16 L1的巨噬细胞表现出增加的UPEC摄取和增强的IL-1β分泌。增加的IL-1β产生依赖于NLRP 3炎性体和半胱天冬酶-1的活化。在体内ATG 16 L1缺陷小鼠的UPEC感染期间，IL-1β分泌也增强，并且IL-1β信号传导的抑制消除了UTI的ATG 16 L1依赖性保护。我们的研究结果表明，ATG 16 L1通常抑制巨噬细胞对UPEC的宿主保护性IL-1β反应。
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 to wild-type macrophages, macrophages deficient in ATG16L1 exhibit increased uptake of UPEC and enhanced secretion of 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.