Kidney intercalated cells are phagocytic and acidify internalized uropathogenic Escherichia coli

Nat Commun. 2021 Apr 23;12(1):2405. doi: 10.1038/s41467-021-22672-5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / chemistry
  • Animals
  • Cells, Cultured
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Gene Expression Profiling / methods
  • Humans
  • Kidney / cytology
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney Tubules, Collecting / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Phagocytes / cytology
  • Phagocytes / immunology*
  • Single-Cell Analysis / methods
  • Uropathogenic Escherichia coli / immunology*
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • Acids
  • Vacuolar Proton-Translocating ATPases