Flagellin Stimulates Protective Lung Mucosal Immunity: Role of Cathelicidin-related Antimicrobial Peptide

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2010 Jun 23

PMID 20566829

Citations 53

Authors

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

Affiliations

Soon will be listed here.

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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