Bacterial flagellin stimulates toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection Journal Article


Authors: Kinnebrew, M. A.; Ubeda, C.; Zenewicz, L. A.; Smith, N.; Flavell, R. A.; Pamer, E. G.
Article Title: Bacterial flagellin stimulates toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection
Abstract: Treatment of vancomycin-resistant Enterococcus (VRE) infections is limited by the paucity of effective antibiotics. Administration of broad-spectrum antibiotics promotes VRE colonization by down-regulating homeostatic innate immune defenses. Intestinal epithelial cells and Paneth cells express antimicrobial factors on direct or indirect stimulation of the Toll-like receptor (TLR)-myeloid differentiation factor 88-mediated pathway by microbederived molecules. Here, we demonstrate that the TLR5 agonist flagellin restores antibiotic-impaired innate immune defenses and restricts colonization with VRE. Flagellin stimulates the expression of Reg III γ, a secreted C-type lectin that kills gram-positive bacteria, including VRE. Systemic administration of flagellin induces Reg III γ expression in intestinal epithelial cells and Paneth cells along the entire length of the small intestine. Induction of Reg III γ requires TLR5 expression in hematopoietic cells and is dependent on interleukin 22 expression. Systemic administration of flagellin to antibiotic-treated mice dramatically reduces VRE colonization. By enhancing mucosal resistance to multidrug-resistant organisms, flagellin administration may provide a clinically useful approach to prevent infections in patients treated with broad-spectrum antibiotics. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Keywords: immunohistochemistry; nonhuman; proteins; mouse; animals; mice; animal tissue; gene expression; animal experiment; animal model; mice, inbred c57bl; cytokines; anti-bacterial agents; western blotting; hematopoietic cell; intestine epithelium cell; innate immunity; immunity, innate; cell count; down regulation; real time polymerase chain reaction; enterococcus; vancomycin resistance; bacterial colonization; vancomycin resistant enterococcus; gram-positive bacterial infections; vancomycin; disease models, animal; small intestine; intestine, small; metronidazole; myeloid differentiation factor 88; multidrug resistance; interleukin 22; interleukins; enterococcal infection; microorganism; neomycin; flagellin; lectin; toll like receptor 5; bacterial flagellum; gram positive bacterium; intestine infection; paneth cell; toll-like receptor 5
Journal Title: Journal of Infectious Diseases
Volume: 201
Issue: 4
ISSN: 0022-1899
Publisher: Oxford University Press  
Date Published: 2010-02-15
Start Page: 534
End Page: 543
Language: English
DOI: 10.1086/650203
PUBMED: 20064069
PROVIDER: scopus
PMCID: PMC2811237
DOI/URL:
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 20 April 2011" - "CODEN: JIDIA" - "Source: Scopus"
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  1. Eric Pamer
    283 Pamer
  2. Nichole I. Smith
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