Host Airway Proteins Interact with<i>Staphylococcus aureus</i>during Early Pneumonia

Ventura, Christy L.; Higdon, Roger; Kolker, Eugene; Skerrett, Shawn J.; Rubens, Craig E.

doi:10.1128/iai.01301-07

Cited by 19 publications

(16 citation statements)

References 48 publications

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“…Complement-mediated opsonization of bacteria may also be augmented by serum amyloid protein P (69), which was also differentially present in the BAL fluids of infected versus mock-infected mice. In a related study, we found that S. aureus was associated with or internalized by 65% of alveolar macrophages within 30 min of infection and by 25% of PMNs after 6 h in the airway; in addition, we found that C3, Ig, and MBL-C were associated with the surface of the bacteria (58). Previous studies by other groups demonstrated that S. aureus was phagocytosed by alveolar macrophages within 30 min following aerosol inoculation as well (18,28,34).…”

Section: Resultsmentioning

confidence: 66%

Staphylococcus aureus Elicits Marked Alterations in the Airway Proteome during Early Pneumonia

et al. 2008

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Pneumonia caused by Staphylococcus aureus is a growing concern in the health care community. We hypothesized that characterization of the early innate immune response to bacteria in the lungs would provide insight into the mechanisms used by the host to protect itself from infection. An adult mouse model of Staphylococcus aureus pneumonia was utilized to define the early events in the innate immune response and to assess the changes in the airway proteome during the first 6 h of pneumonia. S. aureus actively replicated in the lungs of mice inoculated intranasally under anesthesia to cause significant morbidity and mortality. By 6 h postinoculation, the release of proinflammatory cytokines caused effective recruitment of neutrophils to the airway. Neutrophil influx, loss of alveolar architecture, and consolidated pneumonia were observed histologically 6 h postinoculation. Bronchoalveolar lavage fluids from mice inoculated with phosphate-buffered saline (PBS) or S. aureus were depleted of overabundant proteins and subjected to strong cation exchange fractionation followed by liquid chromatography and tandem mass spectrometry to identify the proteins present in the airway. No significant changes in response to PBS inoculation or 30 min following S. aureus inoculation were observed. However, a dramatic increase in extracellular proteins was observed 6 h postinoculation with S. aureus, with the increase dominated by inflammatory and coagulation proteins. The data presented here provide a comprehensive evaluation of the rapid and vigorous innate immune response mounted in the host airway during the earliest stages of S. aureus pneumonia.Staphylococcus aureus is a leading cause of hospital-acquired and health care-associated pneumonia and may be increasing in importance as a cause of severe community-acquired pneumonia. In the inpatient setting, it is the most common grampositive bacterium implicated in cases of ventilator-associated and hospital-acquired pneumonia (1, 9, 31). In addition, S. aureus is a frequent cause of health care-associated pneumonia occurring in residents of long-term-care facilities, individuals recently discharged from acute-care hospitals, and patients receiving outpatient treatment at hospitals and dialysis centers (1, 27, 30). A steady increase in the isolation of methicillinresistant strains of S. aureus from patients with hospital-acquired pneumonia and, more recently, community-acquired pneumonia underscores the importance of identifying host and bacterial factors that facilitate the progression of staphylococcal pneumonia.Mice have been used extensively to study pneumonia caused by a variety of bacteria (2,6,26,35,36,45,55,63,64). Murine models of airborne infection with S. aureus have been useful in characterizing host responses during the first 4 to 8 h of lung infection but do not mimic the natural route of infection and result in self-limited disease, even in immunocompromised animals (28,53,56). In these studies, proinflammatory cytokines and chemokines were released and neutrophils ...

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Section: Resultsmentioning

confidence: 66%

Staphylococcus aureus Elicits Marked Alterations in the Airway Proteome during Early Pneumonia

et al. 2008

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“…SP-A is the principal lung opsonin that associates with S. aureus within 30 min after intranasal infection in mice (67,68). The present and previous studies demonstrate that two members of the collectin family of proteins, SP-A and MBL, are crucial for eradication of acute infections with S. aureus.…”

Section: Cd11cmentioning

confidence: 79%

“…MBL binding to S. aureus cell wall glycoconjugates activates the lectin pathway of complement, enhancing recruitment and clearance of S. aureus through macrophages and neutrophils (69,70). In the lung, however, MBL appears later in inflammatory fluid from the periphery, associating with S. aureus 6 h after infection (67,68). Unlike MBL, SP-A does not bind cell wall glycoconjugates, such as LTA or peptidoglycan, on S. aureus.…”

Section: Cd11cmentioning

confidence: 99%

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

Sever-Chroneos

Krupa

Davis

et al. 2011

Journal of Biological Chemistry

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There is limited knowledge about host factors that facilitate eradication of Staphylococcus aureus infection in the lung. Methicillin-resistant S. aureus has remained a major cause of hospital-and health care-associated pneumonia since its appearance over 40 years ago and has recently become a more prominent etiology in community acquired pneumonia. Colonization of nasal epithelium with S. aureus, a normal occurrence in over 20% of the population, increases the risk for the development of staphylococcal pneumonia (1). Furthermore, S. aureus co-infections are a major complication contributing to high morbidity and mortality during both pandemic and seasonal influenza virus pneumonia (2). S. aureus deploys a combination of virulence factors, including adhesins, toxins, and immunomodulatory molecules, that facilitate infection of different host tissues (3, 4).Surfactant protein A (SP-A) 3 is a crucial component of the pulmonary innate immune system in the alveolar spaces (5, 6). SP-A is the major protein constituent of pulmonary surfactant; it is involved in organization of large aggregate surfactant phospholipids lining the alveolar surface and acts as an opsonin for pathogens (7). SP-A is incorporated in the tubular myelin fraction of pulmonary surfactant that covers the alveolar lining fluid of the distal airway epithelium. The presence of pathogen-derived molecules may trigger reorganization of surfactant lipids (8 -11) and exposure of SP-A to bind pathogens at points of entry on the surfactant interface. Alveolar macrophages in the aqueous hypophase may then patrol areas of disturbance on the surfactant layer binding SP-A-opsonized bacteria. SP-A binds pathogens via a carboxyl-terminal carbohydrate recognition domain in a calcium-dependent manner. Amino-terminal collagen-like and coiled-coil do-

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“…Indeed, proteomic screening for biomarkers has identified many potential biomarkers or expression profiles for ICU-related diseases, such as pulmonary embolism [46], lung infection [47], lung allograft rejection [48], and severe acute respiratory syndrome (SARS) [49].…”

Section: Lung Proteomics In Intensive Carementioning

confidence: 99%