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Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation
- Source :
- Cell Death & Disease, Cell Death and Disease, Cell Death and Disease, Nature Publishing Group, 2017, 8, pp.e2544. 〈10.1038/cddis.2016.476〉, Cell Death and Disease, 2017, 8, pp.e2544. ⟨10.1038/cddis.2016.476⟩, Cell Death and Disease, Nature Publishing Group, 2017, 8, pp.e2544. ⟨10.1038/cddis.2016.476⟩
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Cystic fibrosis (CF), the most common lethal monogenic disease in Caucasians, is characterized by recurrent bacterial infections and colonization, mainly by Pseudomonas aeruginosa, resulting in unresolved airway inflammation. CF is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel in epithelial cells, macrophages, and other cell types. Impaired bacterial handling by macrophages is a feature of CF airways, although it is still debated how defective CFTR impairs bacterial killing. Recent evidence indicates that a defective autophagy in CF macrophages leads to alterations of bacterial clearance upon infection. Here we use bone marrow-derived macrophages from transgenic mice to provide the genetic proof that defective CFTR compromises both uptake and clearance of internalized Pseudomonas aeruginosa. We demonstrate that the proteostasis regulator cysteamine, which rescues the function of the most common F508del-CFTR mutant and hence reduces lung inflammation in CF patients, can also repair the defects of CF macrophages, thus restoring both bacterial internalization and clearance through a process that involves upregulation of the pro-autophagic protein Beclin 1 and re-establishment of the autophagic pathway. Altogether these results indicate that cysteamine restores the function of several distinct cell types, including that of macrophages, which might contribute to its beneficial effects on CF.
- Subjects :
- 0301 basic medicine
Cancer Research
Settore BIO/06
Cystic Fibrosis
Cysteamine
Immunology
Cystic Fibrosis Transmembrane Conductance Regulator
Inflammation
Bone Marrow Cells
Mice, Transgenic
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
medicine.disease_cause
Cystic fibrosis
Microbiology
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Mice
Downregulation and upregulation
medicine
Animals
Humans
Pseudomonas Infections
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Lung
Pseudomonas aeruginosa
[ SDV.BC ] Life Sciences [q-bio]/Cellular Biology
Macrophages
Cell Biology
medicine.disease
Cystic fibrosis transmembrane conductance regulator
3. Good health
030104 developmental biology
Proteostasis
chemistry
Gene Expression Regulation
Chloride channel
biology.protein
Original Article
Beclin-1
cystic fibrosis, CFTR, macrophqges, beclin 1
medicine.symptom
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease, Cell Death and Disease, Cell Death and Disease, Nature Publishing Group, 2017, 8, pp.e2544. 〈10.1038/cddis.2016.476〉, Cell Death and Disease, 2017, 8, pp.e2544. ⟨10.1038/cddis.2016.476⟩, Cell Death and Disease, Nature Publishing Group, 2017, 8, pp.e2544. ⟨10.1038/cddis.2016.476⟩
- Accession number :
- edsair.doi.dedup.....a184075d3f7a8b3a8ed32dab1a965f83