Renal Sodium Gradient Orchestrates a Dynamic Antibacterial Defense Zone.
Berry, Miriam R
Loudon, Kevin W
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Berry, M. R., Mathews, R., Ferdinand, J., Jing, C., Loudon, K. W., Wlodek, E., Dennison, T., et al. (2017). Renal Sodium Gradient Orchestrates a Dynamic Antibacterial Defense Zone.. Cell, 170 (5), 860-874.e19. https://doi.org/10.1016/j.cell.2017.07.022
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.
Kidney, Kidney Medulla, Monocytes, Cell Line, Phagocytes, Urine, Animals, Mice, Inbred C57BL, Humans, Mice, Urinary Tract Infections, Diabetes Insipidus, Sodium, Transcription Factors, Chemokines, Chemokine CCL2, Salinity, Uropathogenic Escherichia coli, Lipopolysaccharide Receptors
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Medical Research Council (MR/K023934/1)
Medical Research Council (MR/N024907/1)
External DOI: https://doi.org/10.1016/j.cell.2017.07.022
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277399
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