Kidney α–intercalated cells and lipocalin 2: defending the urinary tract
Yuxuan Miao, Soman N. Abraham
Yuxuan Miao, Soman N. Abraham
Published June 17, 2014
Citation Information: J Clin Invest. 2014;124(7):2844-2846. https://doi.org/10.1172/JCI76630.
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Commentary

Kidney α–intercalated cells and lipocalin 2: defending the urinary tract

Abstract

A growing body of evidence indicates that the kidneys contribute substantially to immune defense against pathogens in the urinary tract. In this issue, Paragas et al. report that α–intercalated cells (A-ICs) within the nephron collecting duct sense infecting Gram-negative bacteria, resulting in simultaneously secretion of the iron chelating protein lipocalin 2 (LCN2) and protons, which acidify the urine. A-IC–specific LCN2 and proton secretion markedly reduced the ability of infecting uropathogenic E. coli (UPEC) to grow and sustain infection. The capacity of A-ICs to sense and actively promote clearance of infecting bacteria in the lower urinary tract represents a novel function for these specialized kidney cells, which are best known for their role in modulating acid-base homeostasis.

Authors

Yuxuan Miao, Soman N. Abraham

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Figure 1

A-ICs defend against urinary pathogens.

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A-ICs defend against urinary pathogens. (A) Overview of the urinary syst...
(A) Overview of the urinary system. A-ICs within the collecting duct of the kidney secrete both the bacterial static protein LCN2 and protons (H+) in response to bacterial infection. LCN2 from the kidney travels along the ureters to the bladder, where it inhibits bacterial growth. (B) Interaction between UPEC and TLR4 on A-ICs activates NF-κB, which translocates to the nucleus to induce Lcn2 transcription. LCN2 is then secreted into the urinary space, from where it travels to the bladder. (C) In the bladder, UPEC secrete siderophores (Ent) into the urine to bind Fe. LCN2 binds Ent/Fe complexes and delivers them to host cells, such as polymorphonuclear neutrophils (PMNs), for degradation. LCN2-dependant removal of Ent/Fe complexes from urine effectively prevents bacterial iron acquisition, limiting growth.