title: Tracking the immunopathological response to Pseudomonas aeruginosa during respiratory infections.
abstract: Repeated cycles of infections, caused mainly by Pseudomonas aeruginosa, combined with a robust host immune response and tissue injury, determine the course and outcome of cystic fibrosis (CF) lung disease. As the disease progresses, P. aeruginosa adapts to the host modifying dramatically its phenotype; however, it remains unclear whether and how bacterial adaptive variants and their persistence influence the pathogenesis and disease development. Using in vitro and murine models of infection, we showed that P. aeruginosa CF-adaptive variants shaped the innate immune response favoring their persistence. Next, we refined a murine model of chronic pneumonia extending P. aeruginosa infection up to three months. In this model, including CFTR-deficient mice, we unveil that the P. aeruginosa persistence lead to CF hallmarks of airway remodelling and fibrosis, including epithelial hyperplasia and structure degeneration, goblet cell metaplasia, collagen deposition, elastin degradation and several additional markers of tissue damage. This murine model of P. aeruginosa chronic infection, reproducing CF lung pathology, will be instrumental to identify novel molecular targets and test newly tailored molecules inhibiting chronic inflammation and tissue damage processes in pre-clinical studies.
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cigana
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Nicola Ivan
authors.initials: NI
authors.lastname: Lorè
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Riva
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: De Fino
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Spagnuolo
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sipione
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Rossi
authors.affiliation: University Center for Statistics in the Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nonis
authors.affiliation: Department of Pathology and Diagnostics, University Hospital, Verona, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cabrini
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
mesh_terms: D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009894:Opportunistic Infections; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
chemical_list: D018925:Chemokines; D016207:Cytokines