The Marie Skłodowska Curie Action (MSCA) OPTIMISE “Dissecting the molecular pathogenesis of Legionella spp. in human lung models” aimed to establish human Precision-Cut Lung Slices (hPCLS) as physiologically relevant model to study infection by the human bacterial pathogen Legionella pneumophila and related species.
Legionella spp. are environmental bacteria that can infect susceptible individuals and cause a lethal pneumonia known as Legionnaires’ Disease. Aging populations and the increasing use of immune modulatory therapies have given rise to a growing incidence of opportunistic infections caused by pathogens such as Legionella spp..
As for many other infectious diseases, most of our knowledge about the mechanisms driving the outcome of the Legionella-host interaction, originates from studies in cellular and surrogate animal models, which often fail to recapitulate key aspects of human disease. The mechanisms underlying the susceptibility to disease and the virulence of different Legionella isolates in the human lung remain largely elusive. However, as also strikingly highlighted by the current COVID-19 pandemic, understanding disease mechanisms and rapid translation from mechanistic research into new therapies, requires information about the processes occurring in human tissue.
The MSCA OPTIMISE aimed to address this gap in knowledge by 1) optimizing the generation of hPCLS, small uniform slices of human lung tissue from donated human lungs, 2) characterizing their viability, architecture and cellular composition and 3) measuring tissue invasion, growth and pathology induced by different Legionella isolates. Hundreds of these slices can be generated from one human lung, allowing comparison of many bacteria or treatments at the same time in the laboratory. The specific objectives of OPTIMISE were to reveal more about the mechanisms driving 1) host-susceptibility to Legionnaire’s Disease and 2) the virulence of different strains of these environmental bacteria by analyzing the response of the whole tissue, but also of individual lung cells to infection with Legionella.
