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C3 promotes clearance of Klebsiella pneumoniae by A549 epithelial cells

AutorAstorza, Beatriz de; Cortés, Guadalupe; Crespí, Catalina; Saus, Carles; Rojo, José María ; Albertí, Sebastián
Fecha de publicaciónmar-2004
EditorAmerican Society for Microbiology
CitaciónInfection and Immunity, 72 (3) : 1767-1774 (2004)
ResumenThe airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.
The airway epithelium is the largest surface of the respiratory tract and is often the initial site of contact between microbes and their hosts. Through this interaction epithelial cells may have the opportunity to detect and respond to pathogens independently of signals from other cell types of the respiratory system. This is a crucial step for the activation of an efficient inflammatory response and for the recruitment of leukocytes to the lung. However, the capacity of the epithelial cells to detect the respiratory microbial pathogens and directly participate in the defense against them remains poorly investigated. Respiratory epithelia are coated with a thin layer of airway and alveolar secretions. In the nose, trachea, and bronchi, the secretions are, in part, generated by airway epithelial cells (3, 8). In the distal airways and alveoli, Clara cells and type 2 alveolar cells, respectively, are the predominant secretory epithelial cells (8, 19, 26). Antimicrobial polypeptides and local complement are two of the components of the respiratory secretions that may provide an important early clearance mechanism for pathogens before immune cells are recruited and systemic complement can reach the lung (8, 9, 26, 31). Moreover, the initial phase of inflammatory response to infection involves activation of the humoral innate immune system (in particular, the complement). Experimental and clinical observations indicate that suitable levels of complement are critical for efficient detection and clearance of the microorganism from the lung. Complement-depleted animals were unable to clear Streptococcus pneumoniae or Pseudomonas aeruginosa from their lungs as efficiently as healthy animals (9). Moreover, certain mannose-binding genotypes of lectin, a key mediator of innate host immunity that activates the complement cascade, have been associated with an increased risk of invasive pneumonia (20). It is reasonable to believe that these observations were made on the basis of the fact that bacterial opsonization by
complement promotes adhesion and ingestion of microorganisms by professional phagocytes, including alveolar macrophages resident on the epithelial surface and neutrophils recruited to the lung (29). However, to date the role of complement in the interaction between microbes and the first line of immune innate defense, the airway epithelial cells, has not been described. To investigate the role of complement in the interaction between the alveolar epithelial cells and bacteria, we used Klebsiella pneumoniae, a major nosocomial pathogen causing pneumonia (17). Pulmonary infections caused by this opportunistic pathogen are characterized by a rapid progressive clinical course complicated by lung abscesses and multilobular involvement which leaves a short time for the establishment of an effective antibiotic treatment in which the first barriers of defense, like the alveolar epithelial cells and complement, might play a crucial role. We observed that complement, specifically C3, enhanced the bacterium-epithelial-cell interaction. This phenomenon was particularly relevant for the poorly encapsulated bacterial strains, which deposited C3 and were internalized by A549 epithelial cells efficiently but showed a marked reduction in their ability to cause pneumonia compared with encapsulated strains
Descripción8 páginas, 5 figuras -- PAGS nros. 1767-1774
Versión del editorhttp://dx.doi.org/10.1128/​IAI.72.3.1767-1774.2004
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