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The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification.

  • Sedlyarov V CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Eichner R CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Girardi E CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Essletzbichler P CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Goldmann U CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Nunes-Hasler P Department of Cell Physiology and Metabolism, University of Geneva, Geneva 1211, Switzerland.
  • Srndic I CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Moskovskich A CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Heinz LX CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Kartnig F CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Bigenzahn JW CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Rebsamen M CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria.
  • Kovarik P Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), Vienna 1030, Austria.
  • Demaurex N Department of Cell Physiology and Metabolism, University of Geneva, Geneva 1211, Switzerland.
  • Superti-Furga G CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, Vienna 1090, Austria. Electronic address: gsuperti@cemm.oeaw.ac.at.
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  • 2018-05-22
Published in:
  • Cell host & microbe. - 2018
CRISPR screen
NBC3
NBCn1
SLC4A7
intracellular bacterial killing
macrophages
phagocytosis
phagosome acidification
solute carrier
Bicarbonates
CRISPR-Cas Systems
Cation Transport Proteins
Cytoplasm
Gene Knockout Techniques
Homeostasis
Humans
Hydrogen-Ion Concentration
Macrophages
Phagocytosis
Phagosomes
Sodium-Bicarbonate Symporters
THP-1 Cells
Transcriptome
U937 Cells
English Macrophages represent the first line of immune defense against pathogens, and phagosome acidification is a necessary step in pathogen clearance. Here, we identified the bicarbonate transporter SLC4A7, which is strongly induced upon macrophage differentiation, as critical for phagosome acidification. Loss of SLC4A7 reduced acidification of phagocytosed beads or bacteria and impaired the intracellular microbicidal capacity in human macrophage cell lines. The phenotype was rescued by wild-type SLC4A7, but not by SLC4A7 mutants, affecting transport capacity or cell surface localization. Loss of SLC4A7 resulted in increased cytoplasmic acidification during phagocytosis, suggesting that SLC4A7-mediated, bicarbonate-driven maintenance of cytoplasmic pH is necessary for phagosome acidification. Altogether, we identify SLC4A7 and bicarbonate-driven cytoplasmic pH homeostasis as an important element of phagocytosis and the associated microbicidal functions in macrophages.
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  • English
Open access status
hybrid
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https://sonar.ch/global/documents/46690
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