CFTR regulates phagosome acidification in macrophages and alters bactericidal activity

A Di, ME Brown, LV Deriy, C Li, FL Szeto, Y Chen… - Nature cell …, 2006 - nature.com
A Di, ME Brown, LV Deriy, C Li, FL Szeto, Y Chen, P Huang, J Tong, AP Naren, V Bindokas…
Nature cell biology, 2006nature.com
Acidification of phagosomes has been proposed to have a key role in the microbicidal
function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis
transmembrane conductance regulator Cl− channel (CFTR) participates in phagosomal pH
control and has bacterial killing capacity. Alveolar macrophages from Cftr−/− mice retained
the ability to phagocytose and generate an oxidative burst, but exhibited defective killing of
internalized bacteria. Lysosomes from CFTR-null macrophages failed to acidify, although …
Abstract
Acidification of phagosomes has been proposed to have a key role in the microbicidal function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl channel (CFTR) participates in phagosomal pH control and has bacterial killing capacity. Alveolar macrophages from Cftr−/− mice retained the ability to phagocytose and generate an oxidative burst, but exhibited defective killing of internalized bacteria. Lysosomes from CFTR-null macrophages failed to acidify, although they retained normal fusogenic capacity with nascent phagosomes. We hypothesize that CFTR contributes to lysosomal acidification and that in its absence phagolysosomes acidify poorly, thus providing an environment conducive to bacterial replication.
nature.com