The chemokine CCL18 characterises Pseudomonas infections in cystic fibrosis lung disease

Cystic fibrosis (CF) lung disease is characterised by chronic Pseudomonas aeruginosa infection and leukocyte infiltration. Chemokines recruit leukocytes to sites of infection. Gene expression analysis identified the chemokine CCL18 as upregulated in CF leukocytes. We hypothesised that CCL18 characterises infection and inflammation in patients with CF lung disease.Therefore, we quantified CCL18 protein levels in the serum and airway fluids of CF patients and healthy controls, and studied CCL18 protein production by airway cells ex vivo.These studies demonstrated that CCL18 levels were increased in the serum and airway fluids from CF patients compared with healthy controls. Within CF patients, CCL18 levels were increased in P. aeruginosa-infected CF patients. CCL18 levels in the airways, but not in serum, correlated with severity of pulmonary obstruction in CF. Airway cells isolated from P. aeruginosa-infected CF patients produced significantly higher amounts of CCL18 protein compared with airway cells from CF patients without P. aeruginosa infection or healthy controls.Collectively, these studies show that CCL18 levels characterise chronic P. aeruginosa infection and pulmonary obstruction in patients with CF. CCL18 may, thus, serve as a potential biomarker and therapeutic target in CF lung disease.

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CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease

European Respiratory Journal ◽

10.1183/09031936.00173514 ◽

2015 ◽

Vol 46 (2) ◽

pp. 395-404 ◽

Cited By ~ 4

Author(s):

Melanie Carevic ◽

Anurag Singh ◽

Nikolaus Rieber ◽

Olaf Eickmeier ◽

Matthias Griese ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Lung Disease ◽

Immune Cells ◽

Therapeutic Target ◽

Cystic Fibrosis Lung ◽

Fungal Colonisation ◽

Cystic Fibrosis Lung Disease ◽

Potential Biomarker ◽

Healthy Control

Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4+ granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4+ airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease.

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Cell based therapy aides in infection and inflammation resolution in the murine model of cystic fibrosis lung disease

Stem Cell Discovery ◽

10.4236/scd.2013.32019 ◽

2013 ◽

Vol 03 (02) ◽

pp. 139-153 ◽

Cited By ~ 18

Author(s):

Tracey L. Bonfield ◽

Donald Lennon ◽

Santosh K. Ghosh ◽

Amy M. DiMarino ◽

Aaron Weinberg ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Murine Model ◽

Cystic Fibrosis Lung ◽

Cell Based Therapy ◽

Cystic Fibrosis Lung Disease ◽

Infection And Inflammation ◽

Inflammation Resolution

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Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease

Journal of Innate Immunity ◽

10.1159/000446840 ◽

2016 ◽

Vol 8 (6) ◽

pp. 531-540 ◽

Cited By ~ 15

Author(s):

Anjali Ralhan ◽

Julie Laval ◽

Felipe Lelis ◽

Marlene Ballbach ◽

Charlotte Grund ◽

...

Keyword(s):

Cystic Fibrosis ◽

Innate Immunity ◽

Lung Disease ◽

Tissue Injury ◽

Innate Immune ◽

Airway Epithelial ◽

Large Numbers ◽

Cystic Fibrosis Lung Disease ◽

Infection And Inflammation ◽

Bacteria And Fungi

Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. The inflammatory response in CF is dominated by the activation of the innate immune system. Bacteria and fungi represent the key pathogens chronically colonizing the CF airways. In response, innate immune pattern recognition receptors, expressed by airway epithelial and myeloid cells, sense the microbial threat and release chemoattractants to recruit large numbers of neutrophils into CF airways. However, neutrophils fail to efficiently clear the invading pathogens, but instead release harmful proteases and oxidants and finally cause tissue injury. Here, we summarize and discuss current concepts and controversies in the field of innate immunity in CF lung disease, facing the ongoing questions of whether inflammation is good or bad in CF and how innate immune mechanisms could be harnessed therapeutically.

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