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α-intercalated cells defend the urinary system from bacterial infection

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Item Type:Article
Title:α-intercalated cells defend the urinary system from bacterial infection
Creators Name:Paragas, N., Kulkarni, R., Werth, M., Schmidt-Ott, K.M., Forster, C., Deng, R., Zhang, Q., Singer, E., Klose, A.D., Shen, T.H., Francis, K.P., Ray, S., Vijayakumar, S., Seward, S., Bovino, M.E., Xu, K., Takabe, Y., Amaral, F.E., Mohan, S., Wax, R., Corbin, K., Sanna-Cherchi, S., Mori, K., Johnson, L., Nickolas, T., D’Agati, V., Lin, C.S., Qiu, A., Al-Awqati, Q., Ratner, A.J. and Barasch, J.
Abstract:{alpha}–Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC–dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.
Keywords:Acid-Base Equilibrium, Acute-Phase Proteins, Animal Disease Models, Collecting Kidney Tubules, Escherichia coli Infections, Hydrogen-Ion Concentration, Inbred C3H Mice, Inbred C57BL Mice, Iron, Knockout Mice, Lipocalins, Oncogene Proteins, Proto-Oncogene Proteins, Toll-Like Receptor 4, Transgenic Mice, Urinary Tract Infections, Uropathogenic Escherichia coli, Animals, Mice
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:2963-2976
Date:1 July 2014
Additional Information:Erratum in: J Clin Invest 124(12): 5521.
Official Publication:https://doi.org/10.1172/JCI71630
PubMed:View item in PubMed

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