Kidney intercalated cells are phagocytic and acidify internalized uropathogenic Escherichia coli

Vijay Saxena (), Hongyu Gao, Samuel Arregui, Amy Zollman, Malgorzata Maria Kamocka, Xiaoling Xuei, Patrick McGuire, Michael Hutchens, Takashi Hato, David S. Hains and Andrew L. Schwaderer ()
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Vijay Saxena: Indiana University School of Medicine, Department of Pediatrics, Division of Nephrology
Hongyu Gao: Indiana University School of Medicine, Department of Medical & Molecular Genetics
Samuel Arregui: Indiana University School of Medicine, Department of Pediatrics, Division of Nephrology
Amy Zollman: Indiana University School of Medicine, Department of Medicine, Division of Nephrology
Malgorzata Maria Kamocka: Indiana University School of Medicine, Department of Medicine, Division of Nephrology
Xiaoling Xuei: Indiana University School of Medicine, Department of Medical & Molecular Genetics
Patrick McGuire: Indiana University School of Medicine, Department of Medical & Molecular Genetics
Michael Hutchens: Oregon Health and Science University, Department of Anesthesiology & Perioperative Medicine
Takashi Hato: Indiana University School of Medicine, Department of Medicine, Division of Nephrology
David S. Hains: Indiana University School of Medicine, Department of Pediatrics, Division of Nephrology
Andrew L. Schwaderer: Indiana University School of Medicine, Department of Pediatrics, Division of Nephrology

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22672-5

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