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Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide.

Authors
  • Yu, Fu-shin
  • Cornicelli, Matthew D
  • Kovach, Melissa A
  • Newstead, Michael W
  • Zeng, Xianying
  • Kumar, Ashok
  • Gao, Nan
  • Yoon, Sang Gi
  • Gallo, Richard L
  • Standiford, Theodore J
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Jul 15, 2010
Volume
185
Issue
2
Pages
1142–1149
Identifiers
DOI: 10.4049/jimmunol.1000509
PMID: 20566829
Source
Medline
License
Unknown

Abstract

TLRs are required for generation of protective lung mucosal immune responses against microbial pathogens. In this study, we evaluated the effect of the TLR5 ligand flagellin on stimulation of antibacterial mucosal immunity in a lethal murine Pseudomonas aeruginosa pneumonia model. The intranasal pretreatment of mice with purified P. aeruginosa flagellin induced strong protection against intratracheal P. aeruginosa-induced lethality, which was attributable to markedly improved bacterial clearance, reduced dissemination, and decreased alveolar permeability. The protective effects of flagellin on survival required TLR5 and were observed even in the absence of neutrophils. Flagellin induced strong induction of innate genes, most notably the antimicrobial peptide cathelicidin-related antimicrobial peptide. Finally, flagellin-induced protection was partially abrogated in cathelicidin-related antimicrobial peptide-deficient mice. Our findings illustrate the profound stimulatory effect of flagellin on lung mucosal innate immunity, a response that might be exploited therapeutically to prevent the development of gram-negative bacterial infection of the respiratory tract.

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