title: Host genetic diversity influences the severity of Pseudomonas aeruginosa pneumonia in the Collaborative Cross mice.
abstract: BACKGROUND
  Pseudomonas aeruginosa is one of the top three causes of opportunistic infections in humans. Patients with a compromised immune system, due to immunosuppressive therapies or underlying diseases such as cancer, AIDS or the hereditary disease cystic fibrosis, are at risk of developing P. aeruginosa infection. However, clinical evidence indicates extremely variable outcomes of P. aeruginosa infections in individuals at risk, suggesting that host multi-complex genetic traits may influence the severity of this opportunistic infection. Here, we have used an innovative experimental model to dissect whether host genetic background, such as those found in the outbred population, could influence the risk of morbidity and mortality to P. aeruginosa pneumonia.
  
  
  RESULTS
  A highly genetically-diverse mouse resource population, Collaborative Cross (CC) mice, was infected with a clinical strain of P. aeruginosa and subsequently monitored for mortality, mean survival time, and morbidity, change in body weight for seven days post infection. Disease phenotypes ranged from complete resistance and recovery of body weight to lethal disease. Initial variables, including body weight, age and gender, have limited influence on P. aeruginosa outcome, emphasizing the role of host genetic background in defining the risk of morbidity and mortality. When broad-sense heritability of phenotypic traits was evaluated, it confirmed the influence of genetic profile rather than environmental factors among the CC lines during P. aeruginosa infection.
  
  
  CONCLUSIONS
  This innovative model system can potentially reproduce the variables responses of disease severity observed in humans during P. aeruginosa pneumonia. Our results demonstrated that a widely-marked differential response to P. aeruginosa airway infection in term of morbidity and mortality, is mainly affected by host genetic factors, as multiple genetic loci or polymorphic variations.
authors: Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS - San Raffaele Scientific Institute, Milan, Italy. lore.nicolaivan@hsr.it.
authors: Nicola Ivan
authors: NI
authors: Lorè
authors: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel. fuadi@post.tau.ac.il.
authors: Fuad A
authors: FA
authors: Iraqi
authors: Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS - San Raffaele Scientific Institute, Milan, Italy. bragonzi.alessandra@hsr.it.
authors: Alessandra
authors: A
authors: Bragonzi
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D054884:Host-Pathogen Interactions / Q000235:genetics*; D008297:Male; D051379:Mice; D010641:Phenotype; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa; D019655:Quantitative Trait, Heritable; D012720:Severity of Illness Index; D012737:Sex Factors