The nuclear factor kappa-B pathway in airway epithelium regulates neutrophil recruitment and host defence following Pseudomonas aeruginosa infection.

Chen SM, Cheng DS, Williams BJ, Sherrill TP, Han W, Chont M, Saint-Jean L, Christman JW, Sadikot RT, Yull FE, Blackwell TS
Clin Exp Immunol. 2008 153 (3): 420-8

PMID: 18647324 · PMCID: PMC2527362 · DOI:10.1111/j.1365-2249.2008.03707.x

Pseudomonas aeruginosa pneumonia usually results from a deficit of the innate immune system. To investigate whether inflammatory signalling by airway epithelial cells provides a pivotal line of defence against P. aeruginosa infection, we utilized two separate lines of inducible transgenic mice that express a constitutive activator of the nuclear factor kappa-B (NF-kappaB) pathway (IKTA) or a dominant inhibitor of NF-kappaB (DNTA) in airway epithelial cells. Compared with control mice, IKTA mice showed an enhanced host response to P. aeruginosa infection with greater neutrophil influx into the lungs, increased expression of Glu-Leu-Arg-positive (ELR(+)) CXC chemokines macrophage inflammatory protein-2 and keratinocyte chemoattractant (KC), superior bacterial clearance and improved survival at 24 h after infection. Neutrophil depletion abrogated the improvement in host defence identified in IKTA mice. In contrast, DNTA mice showed impaired responses to P. aeruginosa infection with higher bacterial colony counts in the lungs, decreased neutrophilic lung inflammation and lower levels of KC in lung lavage fluid. DNTA mice given recombinant KC at the time of P. aeruginosa infection demonstrated improved neutrophil recruitment to the lungs and enhanced bacterial clearance. Our data indicate that the NF-kappaB pathway in airway epithelial cells plays an essential role in defence against P. aeruginosa through generation of CXC chemokines and recruitment of neutrophils.

MeSH Terms (15)

Animals Bronchoalveolar Lavage Fluid Chemokine CXCL2 Chemokines, CXC Cytokines Disease Models, Animal Epithelium Keratinocytes Lung Mice Mice, Transgenic Neutrophil Infiltration NF-kappa B Pseudomonas aeruginosa Pseudomonas Infections

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