Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000075.xml
Download PDF
Semin Respir Crit Care Med 2003; 24(6): 671-680
DOI: 10.1055/s-2004-815663
DOI: 10.1055/s-2004-815663
Pseudomonas aeruginosa: Role in the Pathogenesis of the CF Lung Lesion
Further Information
Publication History
Publication Date:
15 January 2004 (online)
ABSTRACT
Lung disease is the leading cause of morbidity and mortality in individuals with cystic fibrosis (CF), with P. aeruginosa the main pulmonary infectious agent. Although CF patients can become infected with other microorganisms (such as Burkholderia cepacia complex, Staphylococcus aureus, Haemophilus influenzae, and atypical mycobacteria), P. aeruginosa predominates, eventually infecting ~80% of patients. Once established, P. aeruginosa infection usually persists until death. The interaction between the CF host and this opportunistic pathogen is unique and most likely directly contributes to the classical end-stage pathology of CF lung disease. However, the extent to which this constitutes success by the pathogen or failure by the host, or both, is yet to be determined. Many important questions remain regarding host susceptibility, the role of both innate and adaptive immune defenses, bacterial infectivity and transmission, and pathogen virulence factors. Here, we discuss some recent advances toward understanding this complex interaction between host and pathogen and how the interplay influences the CF lung lesion.
KEYWORDS
Inflammation - airway surface liquid - epithelial cells - {Pseudomonas aeruginosa, cystic fibrosis - biofilm - mucoid - lipopolysaccharide
REFERENCES
- 1 Vankeerberghen A, Cuppens H, Cassiman J. The cystic fibrosis transmembrane conductance regulator: an intriguing protein with peiotropic functions. J Cystic Fibrosis . 2002; 1 13-29
- 2 Maselli J H, Sontag M K, Norris J M, MacKenzie T, Wagener J S, Accurso F J. Risk factors for initial acquisition of Pseudomonas aeruginosa in children with cystic fibrosis identified by newborn screening. Pediatr Pulmonol . 2003; 35 257-262
- 3 Johansen H K, Nir M, Hoiby N, Koch C, Schwartz M. Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation. Lancet . 1991; 337 631-634
- 4 Kubesch P, Dork T, Wulbrand U. et al . Genetic determinants of airways' colonisation with Pseudomonas aeruginosa in cystic fibrosis. Lancet . 1993; 341 189-193
- 5 Lester L A, Kraut J, Lloyd-Still J. et al . Delta F508 genotype does not predict disease severity in an ethnically diverse cystic fibrosis population. Pediatrics . 1994; 93 114-118
- 6 Doring G, Krogh-Johansen H, Weidinger S, Hoiby N. Allotypes of alpha 1-antitrypsin in patients with cystic fibrosis, homozygous and heterozygous for delta F508. Pediatr Pulmonol . 1994; 18 3-7
- 7 Garred P, Pressler T, Madsen H O. et al . Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis. J Clin Invest . 1999; 104 431-437
- 8 Bonfield T L, Panuska J R, Konstan M W. et al . Inflammatory cytokines in cystic fibrosis lungs. Am J Respir Crit Care Med . 1995; 152 2111-2118
- 9 Khan T Z, Wagener J S, Bost T, Martinez J, Accurso F J, Riches D W. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med . 1995; 151 1075-1082
- 10 Armstrong D S, Grimwood K, Carlin J B. et al . Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med . 1997; 156 1197-1204
- 11 Burns J L, Gibson R L, McNamara S. et al . Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis . 2001; 183 444-452
- 12 DiMango E, Ratner A J, Bryan R, Tabibi S, Prince A. Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. J Clin Invest . 1998; 101 2598-2605
- 13 Tabary O, Escotte S, Couetil J P. et al . Relationship between IkappaBalpha deficiency, NFkappaB activity and interleukin-8 production in CF human airway epithelial cells. Pflugers Arch . 2001; 443 (suppl 1) S40-S44
- 14 Scheid P, Kempster L, Griesenbach U. et al . Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence. Eur Respir J . 2001; 17 27-35
- 15 Berger M. Lung inflammation early in cystic fibrosis: bugs are indicted, but the defense is guilty. Am J Respir Crit Care Med . 2002; 165 857-858
- 16 Moser C, Kjaergaard S, Pressler T, Kharazmi A, Koch C, Hoiby N. The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the TH2 type. APMIS . 2000; 108 329-335
- 17 Worgall S, Martushova K, Busch A, Lande L, Crystal R G. Apoptosis induced by Pseudomonas aeruginosa in antigen presenting cells is diminished by genetic modification with CD40 ligand. Pediatr Res . 2002; 52 636-644
- 18 Kikuchi T, Worgall S, Singh R, Moore M A, Crystal R G. Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells. Nat Med . 2000; 6 1154-1159
- 19 Chertov O, Yang D, Howard O M, Oppenheim J J. Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev . 2000; 177 68-78
- 20 Birrer P, McElvaney N G, Rudeberg A. et al . Protease- antiprotease imbalance in the lungs of children with cystic fibrosis. Am J Respir Crit Care Med . 1994; 150 207-213
- 21 Berger M, Sorensen R U, Tosi M F, Dearborn D G, Doring G. Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis. J Clin Invest . 1989; 84 1302-1313
- 22 Vandivier R W, Fadok V A, Hoffmann P R. et al . Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest . 2002; 109 661-670
- 23 Linsdell P, Hanrahan J W. Glutathione permeability of CFTR. Am J Physiol . 1998; 275 C323-C326
- 24 Corvol H, Fitting C, Chadelat K. et al . Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis. Am J Physiol Lung Cell Mol Physiol . 2003; 284 L997-1003
- 25 Saba S, Soong G, Greenberg S, Prince A. Bacterial stimulation of epithelial G-CSF and GM-CSF expression promotes PMN survival in CF airways. Am J Respir Cell Mol Biol . 2002; 27 561-567
- 26 Pilewski J M, Frizzell R A. Role of CFTR in airway disease. Physiol Rev . 1999; 79 S215-S255
- 27 Wine J. The genesis of cystic fibrosis lung disease. J Clin Invest . 1999; 103 309-312
- 28 Guggino W B. Cystic fibrosis and the salt controversy. Cell . 1999; 96 607-610
- 29 Zabner J, Smith J J, Karp P H, Widdicombe J H, Welsh M J. Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro. Mol Cell . 1998; 2 397-403
- 30 Smith J J, Travis S M, Greenberg E P, Welsh M J. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell . 1996; 85 229-236
- 31 Travis S M, Conway B A, Zabner J. et al . Activity of abundant antimicrobials of the human airway. Am J Respir Cell Mol Biol . 1999; 20 872-879
- 32 Goldman M J, Anderson G M, Stolzenberg E D, Kari U P, Zasloff M, Wilson J M. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell . 1997; 88 553-560
- 33 Stutts M J, Canessa C M, Olsen J C. et al . CFTR as a cAMP-dependent regulator of sodium channels. Science . 1995; 269 847-850
- 34 Matsui H, Grubb B R, Tarran R. et al . Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell . 1998; 95 1005-1015
- 35 Worlitzsch D, Tarran R, Ulrich M. et al . Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest . 2002; 109 317-325
- 36 Knowles M R, Robinson J M, Wood R E. et al . Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects. J Clin Invest . 1997; 100 2588-2595
- 37 Gilljam H, Ellin A, Strandvik B. Increased bronchial chloride concentration in cystic fibrosis. Scand J Clin Lab Invest . 1989; 49 121-124
- 38 Hull J, Skinner W, Robertson C, Phelan P. Elemental content of airway surface liquid from infants with cystic fibrosis. Am J Respir Crit Care Med . 1998; 157 10-14
- 39 Verkman A S, Song Y, Thiagarajah J R. Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Am J Physiol Cell Physiol . 2003; 284 C2-15
- 40 Tarran R, Grubb B R, Parsons D. et al . The CF salt controversy: in vivo observations and therapeutic approaches. Mol Cell . 2001; 8 149-158
- 41 Bals R, Weiner D J, Meegalla R L, Accurso F, Wilson J M. Salt-independent abnormality of antimicrobial activity in cystic fibrosis airway surface fluid. Am J Respir Cell Mol Biol . 2001; 25 21-25
- 42 Meng Q H, Springall D R, Bishop A E. et al . Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. J Pathol . 1998; 184 323-331
- 43 Kelley T J, Drumm M L. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest . 1998; 102 1200-1207
- 44 Hancock R E. Peptide antibiotics. Lancet . 1997; 349 418-422
- 45 Li J D, Dohrman A F, Gallup M. et al . Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci USA . 1997; 94 967-972
- 46 Afzelius B A. Ciliary dysfunction. In: Crystal RG, West JB, Weibel ER, Barnes PJ, eds. The Lung: Scientific Foundations New York, NY: Raven Press 1997: 2573-2578
MissingFormLabel
- 47 Puchelle E, Bajolet O, Abely M. Airway mucus in cystic fibrosis. Paediatr Respir Rev . 2002; 3 115-119
- 48 Yeates D B, Sturgess J M, Kahn S R, Levison H, Aspin N. Mucociliary transport in trachea of patients with cystic fibrosis. Arch Dis Child . 1976; 51 28-33
- 49 Regnis J A, Robinson M, Bailey D L. et al . Mucociliary clearance in patients with cystic fibrosis and in normal subjects. Am J Respir Crit Care Med . 1994; 150 66-71
- 50 Saiman L, Prince A. Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells. J Clin Invest . 1993; 92 1875-1880
- 51 de Bentzmann S, Roger P, Dupuit F. et al . Asialo GM1 is a receptor for Pseudomonas aeruginosa adherence to regenerating respiratory epithelial cells. Infect Immun . 1996; 64 1582-1588
- 52 Davies J, Dewar A, Bush A. et al . Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition. Eur Respir J . 1999; 13 565-570
- 53 Davies J C, Stern M, Dewar A. et al . CFTR gene transfer reduces the binding of Pseudomonas aeruginosa to cystic fibrosis respiratory epithelium. Am J Respir Cell Mol Biol . 1997; 16 657-663
- 54 Ichikawa J K, Norris A, Bangera M G. et al . Interaction of Pseudomonas aeruginosa with epithelial cells: identification of differentially regulated genes by expression microarray analysis of human cDNAs. Proc Natl Acad Sci USA . 2000; 97 9659-9664
- 55 Schroeder T H, Zaidi T, Pier G B. Lack of adherence of clinical isolates of Pseudomonas aeruginosa to asialo-GM(1) on epithelial cells. Infect Immun . 2001; 69 719-729
- 56 Jeffery P K, Brain A P. Surface morphology of human airway mucosa: normal, carcinoma or cystic fibrosis. Scanning Microsc . 1988; 2 553-560
- 57 Pier G B, Grout M, Zaidi T S. et al . Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science . 1996; 271 64-67
- 58 Pier G B, Grout M, Zaidi T S. Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung. Proc Natl Acad Sci USA . 1997; 94 12088-12093
- 59 Schroeder T H, Lee M M, Yacono P W. et al . CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-kappa B translocation. Proc Natl Acad Sci USA . 2002; 99 6907-6912
- 60 Schroeder T H, Reiniger N, Meluleni G, Grout M, Coleman F T, Pier G B. Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract. J Immunol . 2001; 166 7410-7418
- 61 Massengale A R, Quinn F J, Williams A, Gallagher S, Aronoff S C. The effect of alginate on the invasion of cystic fibrosis respiratory epithelial cells by clinical isolates of Pseudomonas aeruginosa Exp Lung Res . 2000; 26 163-178
- 62 Grassme H, Kirschnek S, Riethmueller J. et al . CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa Science . 2000; 290 527-530
- 63 Tang H, Kays M, Prince A. Role of Pseudomonas aeruginosa pili in acute pulmonary infection. Infect Immun . 1995; 63 1278-1285
- 64 Scharfman A, Van Brussel E, Houdret N, Lamblin G, Roussel P. Interactions between glycoconjugates from human respiratory airways and Pseudomonas aeruginosa Am J Respir Crit Care Med . 1996; 154 S163-S169
- 65 Abman S H, Ogle J W, Harbeck R J, Butler-Simon N, Hammond K B, Accurso F J. Early bacteriologic, immunologic, and clinical courses of young infants with cystic fibrosis identified by neonatal screening. J Pediatr . 1991; 119 211-217
- 65a Duan K, Duplisea R, Surette M G. The effect of cystic fibrosis normal flora strains on Pseudomonas aeruginosa gene expression. UA-AC Conference on Infectious Diseases 2002; Abstract 24
MissingFormLabel
- 66 Davidson D J, Rolfe M. Mouse models of cystic fibrosis. Trends Genet . 2001; 17 S29-S37
- 67 Coleman F T, Mueschenborn S, Meluleni G. et al . Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc Natl Acad Sci USA . 2003; 100 1949-1954
- 68 Govan J RW, Deretic V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia Microbiol Rev . 1996; 60 539-574
- 69 Parad R B, Gerard C J, Zurakowski D, Nichols D P, Pier G B. Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype. Infect Immun . 1999; 67 4744-4750
- 70 Sherbrock-Cox V, Russell N J. Gacesa, P. The purification and chemical characterisation of the alginate present in extracellular material produced by mucoid strains of Pseudomonas aeruginosa Carbohydr Res . 1984; 135 147-154
- 71 Gacesa P. Bacterial alginate biosynthesis: recent progress and future prospects. Microbiology . 1998; 144 1133-1143
- 72 Boucher J C, Yu H, Mudd M H, Deretic V. Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterisation of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection. Infect Immun . 1997; 65 3838-3846
- 73 Mathee K, Ciofu O, Sternberg C. et al . Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung. Microbiology . 1999; 145(Pt 6) 1349-1357
- 74 Speert D P, Farmer S W, Campbell M E, Musser J M, Selander R K, Kuo S. Conversion of Pseudomonas aeruginosa to the phenotype characteristic of strains from patients with cystic fibrosis. J Clin Microbiol . 1990; 28 188-194
- 75 Baltimore R S, Mitchell M. Immunologic investigations of mucoid strains of Pseudomonas aeruginosa: comparison of susceptibility to opsonic antibody in mucoid and nonmucoid strains. J Infect Dis . 1980; 141 238-247
- 76 Pier G B, Coleman F, Grout M, Franklin M, Ohman D E. Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis. Infect Immun . 2001; 69 1895-1901
- 77 Cabral D A, Loh B A, Speert D P. Mucoid Pseudomonas aeruginosa resists nonopsonic phagocytosis by human neutrophils and macrophages. Pediatr Res . 1987; 22 429-431
- 78 Simpson J A, Smith S E, Dean R T. Scavenging by alginate of free radicals released by macrophages. Free Radic Biol Med . 1989; 6 347-353
- 79 Learn D B, Brestel E P, Seetharama S. Hypochlorite scavenging by Pseudomonas aeruginosa alginate. Infect Immun . 1987; 55 1813-1818
- 80 Bayer A S, Speert D P, Park S. et al . Functional role of mucoid exopolysaccharide (alginate) in antibiotic-induced and polymorphonuclear leukocyte-mediated killing of Pseudomonas aeruginosa Infect Immun . 1991; 59 302-308
- 81 Stiver H G, Zachidniak K, Speert D P. Inhibition of polymorphonuclear leukocyte chemotaxis by the mucoid exopolysaccharide of Pseudomonas aeruginosa Clin Invest Med . 1988; 11 247-252
- 82 Pedersen S S, Kharazmi A, Espersen F, Hoiby N. Pseudomonas aeruginosa alginate in cystic fibrosis sputum and the inflammatory response. Infect Immun . 1990; 58 3363-3368
- 83 Konig B, Pedersen S S, Konig W. Effect of Pseudomonas aeruginosa alginate on Escherichia coli- and Staphylococcus aureus-induced inflammatory mediator release from human cells. Int Arch Allergy Immunol . 1993; 100 144-150
- 84 Nivens D E, Ohman D E, Williams J, Franklin M J. Role of alginate and its O acetylation in formation of Pseudomonas aeruginosa microcolonies and biofilms. J Bacteriol . 2001; 183 1047-1057
- 85 Hentzer M, Teitzel G M, Balzer G J. et al . Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. J Bacteriol . 2001; 183 5395-5401
- 86 Garret E S, Perlegas D, Wozniak D J. Negative control of flagellum synthesis in Pseudomonas aeruginosa is modulated by the alterantive sigma factor AlgT (AlgU). J Bacteriol . 1999; 181 7401-7404
- 87 Mahenthiralingam E, Speert D P. Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum. Infect Immun . 1995; 63 4519-4523
- 88 Lizewski S E, Lundberg D S, Schurr M J. The transcriptional regulator AlgR is essential for Pseudomonas aeruginosa pathogenesis. Infect Immun . 2002; 70 6083-6093
- 89 Firoved A M, Boucher J C, Deretic V. Global genomic analysis of AlgU (se)-dependent promoters (sigmulon) in Pseudomonas aeruginosa and implications for inflammatory processes in cytsic fibrosis. J Bacteriol . 2002; 184 1057-1064
- 90 Firoved A M, Deretic V. Microarray analysis of global gene expression in mucoid Pseudomonas aeruginosa J Bacteriol . 2003; 185 1071-1081
- 91 Costerton J W, Stewart P S, Greenberg E P. Bacterial biofilms: a common cause of persistent infections. Science . 1999; 284 1318-1322
- 92 Singh P K, Schaefer A L, Parsek M R, Moniger T O, Welsh M J, Greenberg E P. Quorom-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature . 2000; 407 762-764
- 93 Whiteley M, Bangera M G, Bumgarner R E. et al . Gene expression in Pseudomonas aeruginosa biofilms. Nature . 2001; 413 860-864
- 94 Drenkard E, Ausubel F M. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature . 2002; 416 740-743
- 95 Rumbaugh K, Griswold P JA, Hamood A N. The role of quorom sensing in the in vivo virulence of Pseudomonas aeruginosa Microbes Infect . 2000; 2 1721-1731
- 96 Erickson D L, Endersby R, Kirkham A. et al . Pseudomonas aeruginosa quorom-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect Immun . 2002; 70 1783-1790
- 97 Alexander C, Rietschel E T. Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res . 2001; 7 167-202
- 98 Chow J C, Young D W, Golenbock D T, Christ W J, Gusovsky F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem . 1999; 274 10689-10692
- 99 Liu P V. Extracellular toxins of Pseudomonas aeruginosa J Infect Dis . 1974; 130(suppl) S94-S99
- 100 Wieland C W, Siegmund B, Senaldi G, Vasil M L, Dinarello C A, Fantuzzi G. Pulmonary inflammation induced by Pseudomonas aeruginosa lipopolysaccharide, phospholipase C, and exotoxin A: role of interferon regulatory factor 1. Infect Immun . 2002; 70 1352-1358
- 101 Rocchetta H L, Burrows L L, Lam J S. Genetics of O-antigen biosynthesis in Pseudomonas aeruginosa Microbiol Mol Biol Rev . 1999; 63 523-553
- 102 Hancock R E, Mutharia L M, Chan L, Darveau R P, Speert D P, Pier G B. Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun . 1983; 42 170-177
- 103 Pier G B, Ames P. Mediatoin of the killing of rough, mucoid isolates of Pseudomonas aeruginosa from patients with cystic fibrosis by the alternative pathway of complement. J Infect Dis . 1984; 150 223-228
- 104 Ernst R K, Yi E C, Guo L. et al . Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa Science . 1999; 286 1561-1565
- 105 Hajjar A M, Ernst R K, Tsai J H, Wilson C B, Miller S I. Human Toll-like receptor 4 recognizes host-specific LPS modificatons. Nat Immunol . 2002; 3 354-359
- 106 Mathiak G, Kabir K, Grass G. et al . Lipopolysaccharides from different bacterial sources elicit disparate cytokine responses in whole blood assays. Int J Mol Med . 2003; 11 41-44
- 107 Koyama S, Sato E, Nomura H. et al . The potential of various lipopolysaccharides to release monocyte chemotactic activity from lung epithelial cells and fibroblasts. Eur Respir J . 1999; 14 545-552