title: Interaction between Pseudomonas aeruginosa and host defenses in cystic fibrosis.
abstract: The major causes of morbidity and mortality in cystic fibrosis are chronic pulmonary obstruction and infection. Mucoid Pseudomonas aeruginosa is the primary pathogen in up to 90% of these patients. Once Pseudomonas organisms colonize the airways, they are virtually never eradicated. No defect in systemic host defense has been elucidated, however, several mechanisms contribute to the breakdown in host defenses that allow persistence of this organism in the endobronchial space. These mechanisms involve both bacterial adaptation to an unfavorable host environment and impaired host response. P aeruginosa adapts to the host by expressing excessive mucoid exopolysaccharide and a less virulent form of lipopolysaccharide. These features make it less likely to cause systemic infection, yet still enable it to resist local host defenses. Mucociliary clearance becomes impaired due to abnormal viscoelastic properties of sputum, squamous metaplasia of the respiratory epithelium, and bronchiectasis. Despite a brisk antibody response to a variety of Pseudomonas antigens, several defects in antibody-mediated opsonophagocytosis have been identified. These include (1) development of antibody isotypes that are suboptimal at promoting phagocytosis, (2) formation of immune complexes that inhibit phagocytosis, and (3) proteolytic fragmentation of immunoglobulins in the endobronchial space. Complement-mediated opsonophagocytosis is also compromised by proteolytic cleavage of complement receptors from the cell surface of neutrophils and complement opsonins from the surface of Pseudomonas. The resultant chronic inflammation and infection lead to eventual obliteration of the airways.
authors.affiliation: Intermountain Cystic Fibrosis Center, University of Utah Medical Center, Salt Lake City 84132.
authors.forename: B C
authors.initials: BC
authors.lastname: Marshall
authors.forename: K C
authors.initials: KC
authors.lastname: Carroll
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001422:Bacterial Adhesion; D003165:Complement System Proteins / Q000276:immunology; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D009079:Mucociliary Clearance; D009504:Neutrophils / Q000502:physiology; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D009895:Opsonin Proteins; D003165:Complement System Proteins