Anion Exchanger 2 Regulates Dectin-1-Dependent Phagocytosis and Killing of Candida albicans

• DOI: 10.1371/journal.pone.0158893
• Publication Date: 2016-07-08T18:02:03Z
• Authors: Katia Urso; Julia F. Charles; Gary E. Shull; Antonios O. Alipr...; Barbara Balestrieri
• Keywords: Zymosan; Bafilomycin; Phagocytic Cell

Anion exchanger 2 (Ae2; gene symbol, Slc4a2) is a plasma membrane Cl-/HCO3- expressed in the gastrointestinal tract, kidney and bone. We have previously shown that Ae2 required for function of osteoclasts, bone resorbing cells macrophage lineage, to maintain homeostatic cytoplasmic pH electroneutrality during acid secretion. Macrophages require endosomal acidification pathogen killing process known as phagocytosis. Chloride thought be principal ion responsible maintaining organelle acidification, but whether exchangers such contribute not known. In this study we investigated role primary macrophages find where it regulates intracellular binding Zymosan, fungal cell wall derivative. Surprisingly, transcription surface expression Dectin-1, major phagocytic receptor Candida albicans (C. albicans) reduced absence Ae2. As consequence, Zymosan-induced Tnfα also impaired Ae2-deficient macrophages. Similar deficiency, pharmacological alkalinization lysosomal with bafilomycin A decreases both Dectin-1 mRNA expression. Finally, demonstrate defective phagocytosis human pathogenic fungus C. albicans. Our results strongly suggest critical factor innate response This represents an important contribution better understanding how clearance regulated.