Pseudomonas aeruginosa: Host defence in lung diseases

Abstract

Lung infections caused by the opportunistic pathogenPseudomonas aeruginosa can present as a spectrum of clinical entities from a rapidly fatal pneumonia in a neutropenic patient to a multi-decade bronchitis in patients with cystic fibrosis. P. aeruginosa is ubiquitous in our environment, and one of the most versatile pathogens studied, capable of infecting a number of diverse life forms and surviving harsh environmental factors. It is also able to quickly adapt to new environments, including the lung, where it orchestrates virulence factors to acquire necessary nutrients, and if necessary, turn them off to prevent immune recognition. Despite these capabilities, P. aeruginosa rarely infects healthy human lungs. This is secondary to a highly evolved host defence mechanism that efficiently removes inhaled or aspirated pseudomonads. Many arms of the respiratory host defence have been elucidated using P. aeruginosa as a model pathogen. Human infections with P. aeruginosa have demonstrated the importance of the mechanical barrier functions including mucus clearance, and the innate immune system, including the critical role of the neutrophilic response. As more models of persistent or biofilm P. aeruginosa infections are developed, the role of the adaptive immune response will likely become more evident. Understanding the pathogenesis of P. aeruginosa, and the respiratory host defence response to it has, and will continue to, lead to novel therapeutic strategies to help patients.Key words: biofilm, innate immunity, mucosal immunity, Pseudomonas aeruginosa, respiratory infection. INTRODUCTIONPseudomonas aeruginosa is a common bacterium found in waterborne environments throughout nature.1 It has a large genome containing a myriad of pathogenic and metabolic capabilities allowing it to infect many organisms, including plants, amoebas, nematodes and vertebrate animals.2 Given its pathogenic potential, it is perhaps surprising that human infections from this organism are not more commonplace. Lung infections caused by P. aeruginosa are limited to patients who are immunocompromised, or who have defective mucociliary clearance, previous epithelial injury or foreign body placement. Given its ubiquitous presence in our environment and pathogenic potential, it is clear that a normally functioning host defence is very well adapted to prevent P. aeruginosa infection. Despite this, P. aeruginosa infections can be devastating in the hospitalized or sick. Understanding the failures of the host defence in these patients will help us understand how P. aeruginosa is converted from a common environmental exposure to a deadly pathogen. PSEUDOMONAS AERUGINOSA RESPIRATORY INFECTIONSPseudomonas aeruginosa rarely infects the human lung without an underlying defect in immunity or mechanical barrier. Clinically, P. aeruginosa infections are frequently classified into 'acute' and 'chronic' infections although the distinctions between these groups are not always clear. New acquisition of P. aeruginosa results in symptomology that prompts...

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