Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia.
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.
Harborview Medical Center, Seattle, WA 98104, USA.
Amy E
AE
Morris
H Denny
HD
Liggitt
Thomas R
TR
Hawn
Shawn J
SJ
Skerrett
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D018932:Chemokine CCL2 / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005407:Flagella / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018932:Chemokine CCL2; D016207:Cytokines; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha