The main cause of cystic fibrosis (CF) lung function decline is the persistent activation of the mucosal immune system of the respiratory tract that, while failing to eradicate initial bacterial infections and to prevent chronic P. aeruginosa infections, promotes tissue damage and pulmonary failure.
In the previous project FFC#18/2020 the researcher demonstrated that Th1/17 cells are selectively increased in CF lungs with P. aeruginosa chronic infection, thus suggesting a potential pathogenic role for these cells. Moreover, they also observed that CF-adapted clinical Pa strains significantly persist within dendritic cells, the professional antigen-presenting cells with a pivotal role in bridging the innate and adaptive immune system, promoting a continuous secretion of pro-inflammatory cytokines involved in pathogenic Th1/17 cells generation and activation.
The aim of this project is to identify the molecular mechanism by which Pa-infected dendritic cells activate the pathogenic arms of the mucosal immune system as well as signaling pathways exclusively activated in pulmonary Th1/17 cells in CF patients chronically infected with Pa.
Finally, this project will converge on the identification of new immune checkpoints and druggable targets, among the altered signaling pathways during the interplay between Pa-infected dendritic cells and pathogenic Th1/17 cells, with the ambitious intent to exclusively affect the harmful arms of the CF mucosal immune system.