title: Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.
abstract: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown.
  
  
  
  As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P . aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes.
  
  
  
  We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studies.
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: De Simone
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Spagnuolo
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nicola Ivan
authors.initials: NI
authors.lastname: Lorè
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cigana
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: De Fino
authors.affiliation: Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA.
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.
authors.forename: Fuad A
authors.initials: FA
authors.lastname: Iraqi
authors.affiliation: Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. bragonzi.alessandra@hsr.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D040641:Quantitative Trait Loci
keywords: Candidate genes; Host susceptibility; Linkage analysis; Murine model; P. aeruginosa; Pneumonia; QTL mapping