From left: Moira Paroni (University of Milan), Clelia Peano (CNR-IRGB), Irene Dusetti (University of Milan).
A study coordinated by the University of Milan and the Institute of Genetic and Biomedical Research of the Research Council of Italy (CNR-IRGB) has identified a new mechanism through which the pathogenic bacterium Pseudomonas aeruginosa reprograms protective Th17 cells into pathogenic ones, contributing to chronic lung inflammation in cystic fibrosis.
Researchers identified and characterized the mechanism by which Pseudomonas aeruginosa, one of the primary pathogens that colonize the lungs of people with cystic fibrosis, subverts the pulmonary immune response. The bacterium reprograms protective Th17 lymphocytes, which are normally involved in defending mucous membranes against infections, into pathogenic Th17 cells. These altered cells are capable of directly causing damage to the lung epithelium and triggering a persistent, unregulated inflammatory response.
By analyzing lung samples from cystic fibrosis patients, the researchers observed an increase in two populations of pathogenic Th17 lymphocytes associated with Pseudomonas aeruginosa lung infections. Furthermore, these cells display distinctive molecular characteristics in cystic fibrosis patients compared to those with other inflammatory lung diseases. Finally, another particularly significant finding emerged: even Pseudomonas aeruginosa strains isolated during the early stages of lung colonization are already capable of promoting the generation of pathogenic Th17 cells, well before acquiring many of the typical traits associated with adapting to a cystic fibrosis lung. The research thus highlights an early phase of the interaction between the bacteria and the adaptive immune system, which could represent an opportunity to intervene before chronic inflammation takes hold.
“The findings identify a new axis between bacterial infection, Th17 cell plasticity, and chronic inflammation. They suggest that selectively targeting the upstream process that leads to the generation of pathogenic Th17 cells could represent a highly important immunomodulation strategy for cystic fibrosis in the future,” explains Moira Paroni from the Department of Biosciences at the University of Milan and co-coordinator of the study.
Clelia Peano from the Institute of Genetic and Biomedical Research of the Research Council of Italy (CNR-IRGB), who co-led the research, concludes: “Our research will continue with the goal of identifying the bacterial determinants and molecular mechanisms responsible for Th17 reprogramming, and understanding how to interfere with this process while preserving the protective functions of the immune response.”
The study brought together expertise in cellular microbiology, immunology, genomics, and bioinformatics, alongside clinical groups whose involvement made it possible to study lung samples from patients with cystic fibrosis.
The research was supported by the Italian Cystic Fibrosis Research Foundation (Fondazione per la ricerca sulla Fibrosi Cistica), the leading organization in Italy specifically dedicated to funding cystic fibrosis research, recognized by the Ministry of University and Research (MUR).
For media information contact:
Clelia Peano
CNR-IRGB
clelia.peano@irgb.cnr.it
Press Office:
Francesca Gorini
Cnr – Press Office Unit
francesca.gorini@cnr.it
