Pseudomonas aeruginosa flagellin and alginate elicit very distinct gene expression patterns in airway epithelial cells: implications for cystic fibrosis disease.
Infection with the opportunistic pathogen Pseudomonas aeruginosa remains a major health concern. Two P. aeruginosa phenotypes relevant in human disease include motility and mucoidy. Motility is characterized by the presence of flagella and is essential in the establishment of acute infections, while mucoidy, defined by the production of the exopolysaccharide alginate, is critical in the development of chronic infections, such as the infections seen in cystic fibrosis patients. Indeed, chronic infection of the lung by mucoid P. aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. We have used Calu-3 human airway epithelial cells to investigate global responses to infection with motile and mucoid P. aeruginosa. The response of airway epithelial cells to exposure to P. aeruginosa motile strains is characterized by a specific increase in gene expression in pathways controlling inflammation and host defense. By contrast, the response of airway epithelia to the stimuli presented by mucoid P. aeruginosa is not proinflammatory and, hence, may not be conducive to the effective elimination of the pathogen. The pattern of gene expression directed by flagellin, but not alginate, includes innate host defense genes, proinflammatory cytokines, and chemokines. By contrast, infection with alginate-producing P. aeruginosa results in an overall attenuation of host responses and an antiapoptotic effect.
Cobb
Laura M
LM
Department of Internal Medicine (Molecular Medicine), Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Mychaleckyj
Josyf C
JC
Wozniak
Daniel J
DJ
López-Boado
Yolanda S
YS
D000208:Acute Disease; D000464:Alginates / Q000302:isolation & purification; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001422:Bacterial Adhesion / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005408:Flagellin / Q000276:immunology* / Q000302:isolation & purification; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D020723:Glucuronic Acid / Q000276:immunology* / Q000302:isolation & purification; D006603:Hexuronic Acids / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D009068:Movement / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000382:microbiology*
D000464:Alginates; D006603:Hexuronic Acids; D005408:Flagellin; D020723:Glucuronic Acid