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.