TLR4 and bacterial infectious disease: The first reference to the relationship between TLR4 and UTIs is found in 2003 by Schilling et al., who demonstrated that TLR4 on stromal and hematopoietic cells, in mice, mediates innate resistance to uropathogenic E. coli. This study is one of the first ones to reveal that bladder epithelial cells play a critical role in TLR4-mediated innate immunity in vivo during a mucosal bacterial infection [24].