Renal Sodium Gradient Orchestrates a Dynamic Antibacterial Defense Zone

Cell. 2017 Aug 24;170(5):860-874.e19. doi: 10.1016/j.cell.2017.07.022. Epub 2017 Aug 10.


Lower urinary tract infections are among the most common human bacterial infections, but extension to the kidneys is rare. This has been attributed to mechanical forces, such as urine flow, that prevent the ascent of bladder microbes. Here, we show that the regional hypersalinity, required for the kidney's urine-concentrating function, instructs epithelial cells to produce chemokines that localize monocyte-derived mononuclear phagocytes (MNPs) to the medulla. This hypersaline environment also increases the intrinsic bactericidal and neutrophil chemotactic activities of MNPs to generate a zone of defense. Because MNP positioning and function are dynamically regulated by the renal salt gradient, we find that patients with urinary concentrating defects are susceptible to kidney infection. Our work reveals a critical accessory role for the homeostatic function of a vital organ in optimizing tissue defense.

Keywords: CCL2; NAFT5; diabetes insipidus; kidney; macrophage; monocyte; salt; sodium; urinary tract infection; uropathogenic E. coli.

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CCL2 / metabolism
  • Chemokines / immunology
  • Diabetes Insipidus
  • Humans
  • Kidney / cytology
  • Kidney / immunology*
  • Kidney Medulla / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / cytology
  • Phagocytes / immunology*
  • Salinity
  • Sodium / metabolism
  • Transcription Factors / genetics
  • Urinary Tract Infections / immunology
  • Urinary Tract Infections / microbiology
  • Urine / chemistry
  • Uropathogenic Escherichia coli / physiology


  • Chemokine CCL2
  • Chemokines
  • Lipopolysaccharide Receptors
  • Nfat5 protein, mouse
  • Transcription Factors
  • Sodium