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Host genetic diversity influences the severity of Pseudomonas aeruginosa pneumonia in the Collaborative Cross mice.

Lorè NI, Iraqi FA, Bragonzi A - BMC Genet. (2015)

Bottom Line: 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.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.This innovative model system can potentially reproduce the variables responses of disease severity observed in humans during P. aeruginosa pneumonia.

View Article: PubMed Central - PubMed

Affiliation: Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS - San Raffaele Scientific Institute, Milan, Italy. lore.nicolaivan@hsr.it.

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.

Conclusion: 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.

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Related in: MedlinePlus

Disease phenotypes in CC mice during P. aeruginosa acute respiratory infection. 17 CC lines and A/J mice of 8–14 weeks old (between 3–7 mice per Line), were inoculated with a 1×106 cfu dose of the P. aeruginosa clinical isolate AA2, and monitored for survival time ST (a) and body weight BW (b) for a period of 7 days after infection
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Fig1: Disease phenotypes in CC mice during P. aeruginosa acute respiratory infection. 17 CC lines and A/J mice of 8–14 weeks old (between 3–7 mice per Line), were inoculated with a 1×106 cfu dose of the P. aeruginosa clinical isolate AA2, and monitored for survival time ST (a) and body weight BW (b) for a period of 7 days after infection

Mentions: CC lines, infected with P. aeruginosa, showed a wide-range of Survival time (ST) ranging from complete resistance (100 % survival after seven days post-infection) to lethal disease (100 % death after 1.5 days), while A/J mice showed an intermediate phenotype (30 % of mortality rate after 7 days post-infection) (Fig. 1a, Additional files 1 and 2). Similarly, CC lines had a wide variation in body weight (BW) response to P. aeruginosa infection: ranging from a 23 % decrease in BW after three days to those showing an almost total recovery of change in BW after five days (Fig. 1b). A/J mice lost 16 % of their change in BW after three days but they did not recover completely after seven days. At day 7 post-infection, bacterial cells were not recovered in the organs (blood, liver and lung) of surviving mice (data not shown), indicating that bacterial clearance is independent from differences in morbidity as assessed by recovery of body weight. These data confirm that different traits of the CC mice resource population express a wide response to P. aeruginosa infection, suggesting the key role of genetic variance on the severity of the clinical outcome.Fig 1


Host genetic diversity influences the severity of Pseudomonas aeruginosa pneumonia in the Collaborative Cross mice.

Lorè NI, Iraqi FA, Bragonzi A - BMC Genet. (2015)

Disease phenotypes in CC mice during P. aeruginosa acute respiratory infection. 17 CC lines and A/J mice of 8–14 weeks old (between 3–7 mice per Line), were inoculated with a 1×106 cfu dose of the P. aeruginosa clinical isolate AA2, and monitored for survival time ST (a) and body weight BW (b) for a period of 7 days after infection
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4551369&req=5

Fig1: Disease phenotypes in CC mice during P. aeruginosa acute respiratory infection. 17 CC lines and A/J mice of 8–14 weeks old (between 3–7 mice per Line), were inoculated with a 1×106 cfu dose of the P. aeruginosa clinical isolate AA2, and monitored for survival time ST (a) and body weight BW (b) for a period of 7 days after infection
Mentions: CC lines, infected with P. aeruginosa, showed a wide-range of Survival time (ST) ranging from complete resistance (100 % survival after seven days post-infection) to lethal disease (100 % death after 1.5 days), while A/J mice showed an intermediate phenotype (30 % of mortality rate after 7 days post-infection) (Fig. 1a, Additional files 1 and 2). Similarly, CC lines had a wide variation in body weight (BW) response to P. aeruginosa infection: ranging from a 23 % decrease in BW after three days to those showing an almost total recovery of change in BW after five days (Fig. 1b). A/J mice lost 16 % of their change in BW after three days but they did not recover completely after seven days. At day 7 post-infection, bacterial cells were not recovered in the organs (blood, liver and lung) of surviving mice (data not shown), indicating that bacterial clearance is independent from differences in morbidity as assessed by recovery of body weight. These data confirm that different traits of the CC mice resource population express a wide response to P. aeruginosa infection, suggesting the key role of genetic variance on the severity of the clinical outcome.Fig 1

Bottom Line: 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.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.This innovative model system can potentially reproduce the variables responses of disease severity observed in humans during P. aeruginosa pneumonia.

View Article: PubMed Central - PubMed

Affiliation: Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS - San Raffaele Scientific Institute, Milan, Italy. lore.nicolaivan@hsr.it.

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus