Investigating the role of the renal sodium gradient in defence against urinary tract infection

Abstract

Background Tissue-resident macrophages and dendritic cells respond to immunological challenges within an organ. The kidney is a unique environment for these cells, with extreme but variable hypersalinity in the medulla, generated by urine concentration mechanisms. Lower urinary tract infections are one of the commonest human bacterial infections, yet renal involvement is rare. Mechanical forces, such as anterograde urine fl ow can be protective. We aimed to determine whether additional tissue-specifi c mechanisms protect the kidney. Methods We characterised macrophages and dendritic cells (mononuclear phagocytes [MNP]) in human kidneys, and evaluated their role in defence against uropathogenic Escherichia coli (UPEC). We used murine models and mouse and human cells in culture to investigate the factors controlling MNP positioning in the medulla and, together with human epidemiological datasets, to determine the importance of the renal sodium gradient in defence against urinary tract infection.