학술논문

Intercalated cell function, kidney innate immunity, and urinary tract infections
Document Type
Review Paper
Source
Pflügers Archiv - European Journal of Physiology: Official Journal of the German Physiological Society. 476(4):565-578
Subject
Collecting duct
Antimicrobial peptide
Urinary tract infection
Urine acidification
Language
English
ISSN
0031-6768
1432-2013
Abstract
Intercalated cells (ICs) in the kidney collecting duct have a versatile role in acid–base and electrolyte regulation along with the host immune defense. Located in the terminal kidney tubule segment, ICs are among the first kidney cells to encounter bacteria when bacteria ascend from the bladder into the kidney. ICs have developed several mechanisms to combat bacterial infections of the kidneys. For example, ICs produce antimicrobial peptides (AMPs), which have direct bactericidal activity, and in many cases are upregulated in response to infections. Some AMP genes with IC-specific kidney expression are multiallelic, and having more copies of the gene confers increased resistance to bacterial infections of the kidney and urinary tract. Similarly, studies in human children demonstrate that those with history of UTIs are more likely to have single-nucleotide polymorphisms in IC-expressed AMP genes that impair the AMP’s bactericidal activity. In murine models, depleted or impaired ICs result in decreased clearance of bacterial load following transurethral challenge with uropathogenic E. coli. A 2021 study demonstrated that ICs even act as phagocytes and acidify bacteria within phagolysosomes. Several immune signaling pathways have been identified in ICs which may represent future therapeutic targets in managing kidney infections or inflammation. This review’s objective is to highlight IC structure and function with an emphasis on current knowledge of IC’s diverse innate immune capabilities.