Acute intratracheal Pseudomonas aeruginosa infection in cystic fibrosis mice is age-independent

Abstract

BackgroundSince the discovery of the human CFTR gene in 1989 various mouse models for cystic fibrosis (CF) have been generated and used as a very suitable and popular tool to approach research on this life-threatening disease. Age related changes regarding the course of disease and susceptibility towards pulmonary infections have been discussed in numerous studies.MethodsHere, we investigated CftrTgH(neoim)Hgu and Cftrtm1Unc-Tg(FABPCFTR)1Jaw/J CF mice and their non-CF littermates during an acute lung infection with Pseudomonas aeruginosa for age dependent effects of their lung function and immune response.Mice younger than three or older than six months were intratracheally infected with P. aeruginosa TBCF10839. The infection was monitored by lung function of the animals using non-invasive head-out spirometry and the time course of physiological parameters over 192 hours. Quantitative bacteriology and lung histopathology of a subgroup of animals were used as endpoint parameters.ResultsAge-dependent changes in lung function and characteristic features for CF like a shallower, faster breathing pattern were observed in both CF mouse models in uninfected state. In contrast infected CF mice did not significantly differ from their non-CF littermates in susceptibility and severity of lung infection in both mouse models and age groups. The transgenic Cftrtm1Unc-Tg(FABPCFTR)1Jaw/J and their non-CF littermates showed a milder course of infection than the CftrTgH(neoim)Hgu CF and their congenic C57Bl/6J non-CF mice suggesting that the genetic background was more important for outcome than Cftr dysfunction.ConclusionsPrevious investigations of the same mouse lines have shown a higher airway susceptibility of older CF mice to intranasally applied P. aeruginosa. The different outcome of intranasal and intratracheal instillation of bacteria implies that infected CF epithelium is impaired during the initial colonization of upper airways, but not in the subsequent response of host defense.

Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors

“…Cystic fibrosis is a multiorgan disease affecting the liver, pancreas, gastrointestinal tract, and lungs; however, pulmonary injury is the main cause of death among CF patients (3)(4)(5).…”

“…The underlying molecular mechanism of CF is mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7 (4,6). The CFTR molecule is a 1,480-amino-acid membrane-bound chloride channel (7).…”

“…The condition, in part, provides a suitable environment for microbial growth, including bacteria, such as Staphylococcus aureus, Haemophilus influenzae, Burkholderia cepacia, and Pseudomonas aeruginosa (11). P. aeruginosa, however, persists in the lungs of over 80% of adults suffering from CF and causes recurrent infection and inflammation (1,4,12).…”

A Mouse Model of Post-Stroke Pneumonia Induced by Intra-Tracheal Inoculation with <b><i>Streptococcus pneumoniae</i></b>

“…Applying the bacteria directly into the trachea provides a more standardized approach and thereby allows for a direct investigation of immunosuppression-induced susceptibility for pneumonia without the confounding effect of variable aspiration. Although intra-tracheal inoculation is widely used in lung research [29,30,31,32], it has been applied only by one study in the neuroimmunology field for the assessment of spinal cord injury-induced immune deficiency [33]. …”

Ventilatory pattern and energy expenditure are altered in cystic fibrosis mice

“…Munder and colleagues (6) reported an increase in respiratory rate in CF mice with a hypomorphic mutation when compared to their wild type littermates. Development of infection and progression of lung disease are known to alter ventilatory patterns (7), but these may not be the only contributors to changes in breathing pattern in CF.…”