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Nature. 2008 Oct 9;455(7214):804-7. doi: 10.1038/nature07250. Epub 2008 Aug 24.

Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits.

Author information

1
Infectious Diseases Service, Department of Medicine, Immunology Program, Sloan-Kettering Institute, New York, New York, USA.

Abstract

Infection with antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a dangerous and costly complication of broad-spectrum antibiotic therapy. How antibiotic-mediated elimination of commensal bacteria promotes infection by antibiotic-resistant bacteria is a fertile area for speculation with few defined mechanisms. Here we demonstrate that antibiotic treatment of mice notably downregulates intestinal expression of RegIIIgamma (also known as Reg3g), a secreted C-type lectin that kills Gram-positive bacteria, including VRE. Downregulation of RegIIIgamma markedly decreases in vivo killing of VRE in the intestine of antibiotic-treated mice. Stimulation of intestinal Toll-like receptor 4 by oral administration of lipopolysaccharide re-induces RegIIIgamma, thereby boosting innate immune resistance of antibiotic-treated mice against VRE. Compromised mucosal innate immune defence, as induced by broad-spectrum antibiotic therapy, can be corrected by selectively stimulating mucosal epithelial Toll-like receptors, providing a potential therapeutic approach to reduce colonization and infection by antibiotic-resistant microbes.

PMID:
18724361
PMCID:
PMC2663337
DOI:
10.1038/nature07250
[Indexed for MEDLINE]
Free PMC Article

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