Tumor Necrosis Factor Alpha- and Inducible Nitric Oxide Synthase-Producing Dendritic Cells Are Rapidly Recruited to the Bladder in Urinary Tract Infection but Are Dispensable for Bacterial Clearance

Abstract

The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b ⁺ F4/80 ⁺ CD8 ⁻ Gr-1 ⁻ myeloid subtype. Also, tumor necrosis factor alpha (TNF-α)- and inducible nitric oxide synthase (iNOS)-producing CD11b ^INT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2 ^−/− mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-α-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.