Pseudomonas aeruginosa induced acute emphysema through bacterial secretion in mice

Abstract

Pulmonary emphysema is the major pathological feature of chronic obstructive pulmonary disease (COPD). Although the pathogenesis of emphysema is still not completely understood, but until now a bacterial cause has not really been considered. Recently, we found that the secretion from Pseudomonas aeruginosa could cause severe lung emphysema in mice rapidly. Since the bacterium is ubiquitous and secrets proteases, we hypothesized that direct P. aeruginosa airway infection would have a similar effect. To address this issue, we applied a unilateral lung injury model. First, we observed the dynamic pathophysiology change of acute emphysema. P. aeruginosa secretion was extracted and instilled intratracheally into the left lungs of C57BL/6 and C3H/HeJ mice, while the right lungs were saved as self-control. Alveolar diameter and lung compliance were measured. Later, we tested the effect of P. aeruginosa inoculation in normal C57BL/6 mice, immunosuppressed C57BL/6 mice, and C3H/HeJ (TLR4 deficient) mice. P. aeruginosa secretion extract caused acute panacinar emphysema and decreased dynamic lung compliance. Different types of emphysema are transformable. However, the P. aeruginosa infection could only elicit emphysema in immunosuppressed C57BL/6 mice and C3H/HeJ mice, indicating that normal immunity is essential to protect the hosts from emphysema. Emphysema induced by P. aeruginosa in mice recapitulates all the main features of human emphysema and COPD. Our finding filled a major gap in COPD pathogenesis. We believe P. aeruginosa is the underlying cause of COPD.