Sedlyarov V Eichner R Girardi E Essletzbichler P Goldmann U Nunes-Hasler P Srndic I Moskovskich A Heinz LX Kartnig F Bigenzahn JW Rebsamen M Kovarik P Demaurex N Superti-Furga G 2018 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. application/pdf https://sonar.ch/global/documents/46690 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.chom.2018.04.013 info:eu-repo/semantics/altIdentifier/pmid/29779931 info:eu-repo/semantics/openAccess 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 The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. http://purl.org/coar/resource_type/c_6501