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

Cell Host Microbe. 2018 Jun 13;23(6):766-774.e5. doi: 10.1016/j.chom.2018.04.013. Epub 2018 May 17.


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.

Keywords: CRISPR screen; NBC3; NBCn1; SLC4A7; intracellular bacterial killing; macrophages; phagocytosis; phagosome acidification; solute carrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bicarbonates / metabolism*
  • CRISPR-Cas Systems
  • Cation Transport Proteins / metabolism
  • Cytoplasm / metabolism
  • Gene Knockout Techniques
  • Homeostasis
  • Humans
  • Hydrogen-Ion Concentration
  • Macrophages / metabolism*
  • Phagocytosis
  • Phagosomes / metabolism*
  • Sodium-Bicarbonate Symporters / genetics
  • Sodium-Bicarbonate Symporters / physiology*
  • THP-1 Cells
  • Transcriptome
  • U937 Cells


  • Bicarbonates
  • Cation Transport Proteins
  • SLC4A7 protein, human
  • Sodium-Bicarbonate Symporters