Host Defense Mechanisms Against Pneumonia Due to Pseudomonas aeruginosa

Pennington, James E.; Ehrie, M; Hickey, William F.

doi:10.1093/clinids/6.supplement_3.s657

Cited by 11 publications

(4 citation statements)

References 29 publications

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“…Furthermore, we found that in the absence of ExoU, phagocytes are required for clearance of P. aeruginosa from the lung over the first 12 h of infection. These data are consistent with reports indicating that neutrophils are an essential component of the host response to P. aeruginosa (35,49,58,59) and with clinical observations of increased susceptibility to P. aeruginosa infection in patients with neutropenia (43). Overall, our data provide further validation of the importance of phagocytes in the host response to P. aeruginosa.…”

Section: Discussionsupporting

confidence: 92%

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia

et al. 2008

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Hospital-acquired bacterial pneumonia is a common and serious complication of modern medical care. Many aspects of such infections remain unclear, including the mechanisms by which invading pathogens resist clearance by the innate immune response and the tendency of the infections to be polymicrobial. Here, we used a mouse model of infection to show that Pseudomonas aeruginosa, a leading cause of hospital-acquired pneumonia, interferes with the ability of recruited phagocytic cells to eradicate bacteria from the lung. Early in infection, phagocytic cells, predominantly neutrophils, are recruited to the lungs but are incapacitated when they enter the airways by the P. aeruginosa toxin ExoU. The resulting paucity of functioning phagocytes allows P. aeruginosa to persist within the lungs and results in local immunosuppression that facilitates superinfection with less-pathogenic bacteria. Together, our results provide explanations for previous reports linking ExoU-secreting P. aeruginosa with more severe pulmonary infections and for the tendency of hospital-acquired pneumonia to be polymicrobial.Hospital-acquired pneumonia (HAP) is a common and frequently lethal complication of admission to an acute medical care facility. HAP infections occur in 0.5 to 2% of hospitalized patients (30,33) and are associated with mortality rates of approximately 30% (6,13,41,54). HAP is usually caused by bacterial pathogens, and in 26 to 67% of cases the etiology is polymicrobial (3,8,39). While the reasons for this are unclear, the coexistence of multiple species of bacteria within the lungs of patients may contribute to the high mortality associated with this disease.The gram-negative bacterium Pseudomonas aeruginosa is the leading cause of HAP in patients undergoing mechanical ventilation (referred to as ventilator-associated pneumonia [VAP]) (40). Interestingly, infection with P. aeruginosa, as opposed to infection with most other bacterial species, is an independent risk factor for death in patients with VAP (23). Although a high incidence of antibiotic resistance among P. aeruginosa strains contributes to the excess mortality associated with this bacterium, its intrinsic virulence also likely plays a role. Even VAP patients treated with antimicrobial agents to which their P. aeruginosa isolates were susceptible had a relapse rate of 18% (42). This suggests that P. aeruginosa elaborates potent virulence determinants that are adept at neutralizing the host immune response, resulting in persistent bacterial infections with poor outcomes.Despite the severity of HAP caused by P. aeruginosa, much remains unknown about the mechanisms by which this bacterium persists in the lungs and causes the tissue damage and inflammation associated with pneumonia. P. aeruginosa elaborates a number of virulence factors that may augment the disease process (12, 45), including a type III secretion system, which has been associated with more-severe disease in patients with HAP (18,44). Via a type III secretion system, some strains of P. aeruginosa injec...

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Section: Discussionsupporting

confidence: 92%

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia

et al. 2008

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“…The uptake of [5,6,8,9,11,12,14,15-3H]arachidonic acid by PMNL was 86.5 + 4.7% (n = 5) after 1 h of incubation with the label. Production of LTB4 and 5-HETE by PMNL incubated with either pyocyanin or 1-OHP was inhibited in a dose-dependent manner.…”

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confidence: 98%

“…LTB4 is rapidly metabolized by PMNL to 20-hydroxy-LTB4 and 20carboxy-LTB4 (17). PMNL are also involved directly in the clearance of foreign organisms from the host (11).…”

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confidence: 99%

Production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by human neutrophils is inhibited by Pseudomonas aeruginosa phenazine derivatives

Müller

Sorrell

1991

Infect Immun

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Pyocyanin, a phenazine pigment produced by Pseudomonas aeruginosa, and its metabolite 1-hydroxyphenazine inhibited leukotriene B4 and 5-hydroxyeicosatetraenoic acid production by up to 70% in human neutrophils stimulated with the calcium ionophore A23187 (5 ,uM). This potential anti-inflammatory effect was dose dependent and occurred at low concentrations (10 to 50 ,uM) that did not inhibit neutrophil viability.

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“…The single and most important factor of pulmonary defense against Pseudomonas infection is an adequate population of phagocytic leukocytes (11). The findings of numerous neutrophils in the bronchial secretion often provide the general and useful information concerning the degree of inflammation present (2).…”

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confidence: 99%

Neutrophil Response to Pseudomonas aeruginosa in Respiratory Infection

Ahmed

Dai

Ichinose

et al. 1993

Microbiology and Immunology

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Sputum from patients with acute exacerbation of respiratory infection by Pseudomonas aeruginosa was observed under the electron microscope. External to the cell wall of P. aeruginosa a granular, electron-dense material was observed which is suggestive of capsule. It is supposed that stabilization of capsule occurred by the host antibody, which was produced due to chronic infection by P. aeruginosa. Mucoid type of microcolonies were observed with a fibrous matrix of exopolysaccharide. Other types of microcolonies were surrounded by granular substances or fine fibers. Neutrophil was found to be partially surrounding the microcolony in an attempt to defense. Debris was formed mainly by the destruction of the neutrophil. Most neutrophils were found full of phagocytosed debris; in contrast only a few neutrophils were found to have phagocytosed P. aeruginosa. This study concludes that instead of phagocytosing bacteria, neutrophil phagocytosed debris and bacteria were not completely eradicated.Therefore, this might be one of the factors in the pathogenesis of respiratory infection and persistent colonization by P. aeruginosa.

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Host Defense Mechanisms Against Pneumonia Due to Pseudomonas aeruginosa

Cited by 11 publications

References 29 publications

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia

Pseudomonas aeruginosa Induces Localized Immunosuppression during Pneumonia

Production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by human neutrophils is inhibited by Pseudomonas aeruginosa phenazine derivatives

Neutrophil Response to Pseudomonas aeruginosa in Respiratory Infection

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