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Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia.
Title | Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Morris, AE, H Liggitt, D, Hawn, TR, Skerrett, SJ |
Journal | Am J Physiol Lung Cell Mol Physiol |
Volume | 297 |
Issue | 6 |
Pagination | L1112-9 |
Date Published | 2009 Dec |
ISSN | 1522-1504 |
Keywords | Animals, Bronchoalveolar Lavage Fluid, Cell Count, Chemokine CCL2, Cytokines, Female, Flagella, Immunity, Innate, Inflammation, Lung, Male, Mice, Mice, Inbred C57BL, Neutrophils, Pneumonia, Pseudomonas aeruginosa, Pseudomonas Infections, Toll-Like Receptor 5, Tumor Necrosis Factor-alpha |
Abstract | Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and an important pathogen in patients with chronic lung disease, such as cystic fibrosis and bronchiectasis. The contribution of Toll-like receptor 5 (TLR5) to the innate immune response to this organism is incompletely understood. We exposed wild-type and TLR5-deficient (Tlr5(-/-)) mice to aerosolized P. aeruginosa at low and high inocula and assessed bacterial clearance, lung inflammation, and cytokine production 4 and 24 h after infection. Bacterial clearance was impaired in Tlr5(-/-) mice after low-inoculum, but not high-inoculum, infection. Early bronchoalveolar accumulation of neutrophils was reduced in Tlr5(-/-) mice after low- and high-dose infection. Cytokine responses, including markedly impaired monocyte chemoattractant protein-1 production 4 h after low- and high-inoculum challenge, were selectively altered in Tlr5(-/-) mice. In contrast, there was no impairment of bacterial clearance, neutrophil recruitment, or monocyte chemoattractant protein-1 production in Tlr5(-/-) mice after infection with a nonflagellated isotypic strain of P. aeruginosa. Thus TLR5-mediated recognition of flagellin is involved in activating pulmonary defenses against P. aeruginosa and contributes to antibacterial resistance in a manner that is partially inoculum dependent. These data are the first to demonstrate a unique role for TLR5 in the innate immune response to P. aeruginosa lung infection. |
DOI | 10.1152/ajplung.00155.2009 |
Alternate Journal | Am. J. Physiol. Lung Cell Mol. Physiol. |
PubMed ID | 19801452 |