4.8 Article

Kidney intercalated cells are phagocytic and acidify internalized uropathogenic Escherichia coli

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22672-5

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Funding

  1. National Institute of Diabetes and Digestive and Kidney Diseases [R01DK106286]
  2. Eli Lily Foundation
  3. Indiana Clinical and Translational Sciences Institute (CTSI) - NIH [UL1TR002529]

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Kidney intercalated cells play a role in acid-base homeostasis and exhibit characteristics of professional phagocytes, capable of engulfing and acidifying internalized bacteria, similar to macrophages.
Kidney intercalated cells are involved in acid-base homeostasis via vacuolar ATPase expression. Here we report six human intercalated cell subtypes, including hybrid principal-intercalated cells identified from single cell transcriptomics. Phagosome maturation is a biological process that increases in biological pathway analysis rank following exposure to uropathogenic Escherichia coli in two of the intercalated cell subtypes. Real time confocal microscopy visualization of murine renal tubules perfused with green fluorescent protein expressing Escherichia coli or pHrodo Green E. coli BioParticles demonstrates that intercalated cells actively phagocytose bacteria then acidify phagolysosomes. Additionally, intercalated cells have increased vacuolar ATPase expression following in vivo experimental UTI. Taken together, intercalated cells exhibit a transcriptional response conducive to the kidney's defense, engulf bacteria and acidify the internalized bacteria. Intercalated cells represent an epithelial cell with characteristics of professional phagocytes like macrophages. Kidney intercalated cells are involved in acid-base homeostasis in the kidneys. Here, the authors use single cell transcriptomics and find that interalated cells exhibit a transcriptional response conducive to defense and can engulf and acidify internalized bacteria, similarly to professional phagocytes.

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