Development and Characterization of a Long-Term Murine Model of Streptococcus pneumoniae Infection of the Lower Airways

Chronic obstructive pulmonary disease (COPD) is characterized by long periods of stable symptoms, but exacerbations occur, which result in a permanent worsening of symptoms. Previous studies have shown a link between bacterial colonization of the lower airways of COPD sufferers and an increase in exacerbation frequency. One of the most frequent bacterial colonizers is Streptococcus pneumoniae. To mimic this aspect of COPD, a murine model of low-level pneumococcal colonization in the lung has been developed, in which S. pneumoniae persisted in the lungs for at least 28 days. From day 14 postinfection, bacterial numbers remained constant until at least 28 days postinfection, and animals showed no outward signs of disease. The bacterial presence correlated with a low-level inflammatory response that was localized to small foci across the left and inferior lobes of the lung. The cellular response was predominantly monocytic, and focal fibroplasia was observed at the airway transitional zones. Physiological changes in the lungs were investigated with a Forced Maneuvers system. This new model provides a means of study of a long-term pulmonary infection with a human pathogen in a rodent system. This is an excellent tool for the development of future models that mimic complex respiratory diseases such as COPD and asthma.