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.
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Acknowledgements
This work was supported by National Institutes of Health (NIH) and the National Institute of General Medical Sciences (NIGMS) (R01 GM36823), the Cystic Fibrosis Foundation (Nelson03G0) and the University of Chicago DDRCC (DK42086). The authors wish to thank L. Lester, Director of the Cystic Fibrosis Center at the University of Chicago for many helpful discussions.
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A.D., M.E.B., L.V.D., C.L., F.L.S., Y.C., P.H. and J.K. performed experiments, A.P.N. and V.B. designed and performed immunochemical and fluorescence labelling experiments, H.C.P. and D.J. designed the study and wrote the paper with input from the other authors.
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Di, A., Brown, M., Deriy, L. et al. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol 8, 933–944 (2006). https://doi.org/10.1038/ncb1456
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DOI: https://doi.org/10.1038/ncb1456
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