Abstract
Asthma is a complex respiratory disease, which is associated with reversible airflow obstruction and persistent airway inflammation. A hallmark of severe asthma is the presence of a low level bacterial infection in the lower airways with pathogens such as Streptococcus pneumoniae. Until now this low-level pulmonary bacterial infection has not been mimicked in mice with human pathogens due to mice either clearing the infection within a few days or succumbing to the infection (Stevenson et al. Pharmacol. Ther., 2011; 130:93-105). A new model of prolonged low-level bacterial infection in the lungs of mice with S. pneumoniae will be described. The use of this model in conjunction with the chronic ovalbumin allergic inflammation model aims to understand the mechanism behind bacterial exacerbations in asthma.
An ovalbumin model was optimised in inbred mice. Mice were sensitised intraperitoneally at 0 and 14 days and challenged intranasally at day 21. S. pneumoniae was intranasally instilled before, after or in between the two ovalbumin sensitisations. Physiological and cellular endpoints were evaluated 48 hours after ovalbumin challenge.
The combination of a low-grade bacterial infection in addition to an ovalbumin sensitisation/challenge model skewed the inflammatory profile towards a more Th1 phenotype. The degree of skewing was dependent on when the infection was instilled in relation to ovalbumin sensitisation. Thus demostrating that we have a more clinically relevant model of severe respiratory disease, which could be used to better understand how bacterial infection contribute to the pathogenesis of diseases such as asthma.
- © 2013 ERS