P. aeruginosa Infection in Cystic Fibrosis Could Be Treated Using Novel Gene Therapies

Ana Pamplona, PhD avatar

by Ana Pamplona, PhD |

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CF study

New research has revealed potential, new strategies to fight against Paeruginosa infection and improve both survival and quality of life in patients with cystic fibrosis. The study, entitled “Normal and Cystic Fibrosis Human Bronchial Epithelial Cells Infected with Pseudomonas aeruginosa Exhibit Distinct Gene Activation Patterns” was published in the PLOS ONE journal by researchers from INSERM and Sorbonne Universités, Paris, France.

Cystic fibrosis (CF) is a genetic disease that affects various organs and is characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which results in regular infective pulmonary exacerbations with opportunistic pathogens, such as Pseudomonas aeruginosa (P. aeruginosa). In cystic fibrosis patients, P. aeruginosa is not eliminated from the lower respiratory tract and induces epithelial inflammation that ultimately causes tissue damage. However, the association between CF airway inflammation and this infection is still not well understood.

In this study, the research team hypothesized that Paeruginosa infection induced a strong inflammatory response and established a chronic infection in the CF epithelial cells. To test this hypothesis, they compared the transcriptomic response to Paeruginosa infection in cystic fibrosis and normal epithelial airway cells.

The data showed that P. aeruginosa infection induced in the CF respiratory epithelium higher production, depending on the time of infection, of several proteins involved in the inflammatory response, such as TNF, CSF2, CSF3, CCL2, MMP1, and MMP10, when compared to healthy control cells. Contrary to CF cells, genes beneficial for tissue integrity were activated in healthy control epithelial cells after P. aeruginosa infection. Notably, the results of downregulated and upregulated genes in infected CF cells may lead to a better understanding of mechanisms associated, respectively, to the persistence of P. aeruginosa and the inflammatory response in the CF lung. However, this study has one limitation, which is the overall difference between the mean ages of the patients and the healthy individuals that may impact their response against the pathogen.

The authors plan to analyze the results of manipulating the expression of the genes that were differentially regulated in cystic fibrosis and healthy cells, using them as readout markers for inflammation and antimicrobial activity. The expected results may lead to potential new approaches to fight P. aeruginosa infection and its pathological consequences for CF patients.