PURPOSE: Hospital-acquired bacterial pneumonia is a common and serious complication of admission to an acute medical care facility. Many aspects of these infections remain unclear, such as the mechanisms by which invading pathogens resist clearance by the innate immune response and the propensity of these infections to be polymicrobial. We investigated the mechanism by which Pseudomonas aeruginosa, a leading cause of hospital-acquired pneumonia, avoids eradication by the innate immune response during early disease.
METHODS: A mouse model of pneumonia and in vitro co-incubation of bacteria with human neutrophils were used to characterize interactions between P. aeruginosa and host inflammatory cells.
RESULTS: Early in infection, neutrophils were recruited to the lungs but were killed upon entering the airways by the P. aeruginosa toxin ExoU. The phospholipase activity of ExoU was necessary for this effect. The resulting paucity of functioning neutrophils allowed persistence of P. aeruginosa within the lungs and resulted in local immunosuppression that facilitates superinfection with less pathogenic bacteria.
CONCLUSION: The P. aeruginosa toxin ExoU kills neutrophils, thereby facilitating bacterial persistence during early pneumonia and causing localized immunosuppression in the lungs that predisposes to superinfections.
CLINICAL IMPLICATIONS: The P. aeruginosa toxin ExoU kills neutrophils, thereby facilitating bacterial persistence during early pneumonia and causing localized immunosuppression in the lungs that predisposes to superinfections.
DISCLOSURE: Alan Hauser, No Financial Disclosure Information; No Product/Research Disclosure Information