TY - JOUR
T1 - Flagellin stimulates protective lung mucosal immunity
T2 - Role of cathelicidin-related antimicrobial peptide
AU - Yu, Fu Shin
AU - Cornicelli, Matthew D.
AU - Kovach, Melissa A.
AU - Newstead, Michael W.
AU - Zeng, Xianying
AU - Kumar, Ashok
AU - Gao, Nan
AU - Yoon, Sang Gi
AU - Gallo, Richard L.
AU - Standiford, Theodore J.
PY - 2010/7/15
Y1 - 2010/7/15
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.1000509
DO - 10.4049/jimmunol.1000509
M3 - Article
C2 - 20566829
AN - SCOPUS:77955494032
VL - 185
SP - 1142
EP - 1149
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -