title: The host genetic background defines diverse immune-reactivity and susceptibility to chronic Pseudomonas aeruginosa respiratory infection.
abstract: Patients with P. aeruginosa airways infection show markedly variable clinical phenotypes likely influenced by genetic backgrounds. Here, we investigated the cellular events involved in resistance and susceptibility to P. aeruginosa chronic infection using genetically distinct inbred mouse strains. As for patients, different murine genotypes revealed variable susceptibility to infection. When directly compared, resistant C3H/HeOuJ and susceptible A/J strains revealed distinct immune responsiveness to the pathogen. In C3H/HeOuJ resistant mice, IL17-producing cells rapidly and transiently infiltrated the infected lung, and this was paralleled by the acute accumulation of alveolar macrophages, bacterial clearance and resolution of infection. In contrast, A/J susceptible mice revealed a more delayed and prolonged lung infiltration by IL17+and IFNγ+cells, persistence of innate inflammatory cells and establishment of chronic infection. We conclude that the host genetic background confers diverse immunoreactivity to P. aeruginosa and IL17-producing cells might contribute to the progress of chronic lung infection.
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Spagnuolo
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: De Simone
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Nicola Ivan
authors.initials: NI
authors.lastname: Lorè
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: De Fino
authors.affiliation: Lymphocyte activation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Basso
authors.affiliation: Lymphocyte activation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mondino
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cigana
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
mesh_terms: D000818:Animals; D060467:Disease Resistance; D000068617:Genetic Background; D020022:Genetic Predisposition to Disease; D020381:Interleukin-17 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D011552:Pseudomonas Infections / Q000235:genetics* / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000276:immunology*
chemical_list: D020381:Interleukin-17