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

Fu Shin Yu, Matthew D. Cornicelli, Melissa A. Kovach, Michael W. Newstead, Xianying Zeng, Ashok Kumar, Nan Gao, Sang Gi Yoon, Richard L. Gallo, Theodore J. Standiford

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1142-1149
Number of pages8
JournalJournal of Immunology
Volume185
Issue number2
DOIs
StatePublished - Jul 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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