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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