Document Detail

Toll-like receptor 4 facilitates binding of Shiga toxin to colon carcinoma and primary umbilical vein endothelial cells.
MedLine Citation:
PMID:  21054580     Owner:  NLM     Status:  In-Process    
Infection with Shiga toxin (Stx)-producing, gram-negative bacteria can induce serious conditions such as dysentery and hemolytic uremic syndrome. In target cells, Stx is internalized by endocytosis, and travels through the Golgi apparatus and the endoplasmic reticulum to reach the cytosol, where it inhibits protein synthesis. Toll-like receptor 4 (TLR4) mediates the recognition of gram-negative bacteria. Here, we have investigated whether the cellular uptake and transport of Stx could involve TLR4. We found that upon small interfering RNA (siRNA)-mediated TLR4 depletion in epithelial colon carcinoma cells, Stx transport to the Golgi was strongly reduced, and this was primarily caused by diminished Stx cellular binding rather than by reduction in toxin uptake or endosome-to-Golgi transport. The reduced cellular binding of Stx upon siRNA-transfection was solely due to TLR4 depletion, because reconstitution of TLR4 expression by the introduction of an siRNA-resistant TLR4 gene completely abolished the TLR4-targeting siRNA-mediated effect. Importantly, the effect of TLR4 depletion was not restricted to cancer cells or epithelial cells, because primary human umbilical vein endothelial cells also displayed reduced Stx binding upon TLR4 depletion. These results indicate that although TLR4 is imperative in innate immunity against gram-negative bacteria, it may be exploited by bacterial toxins, for example Stx, to gain access and entry into cells.
Maria L Torgersen; Nikolai Engedal; Anne-Mari G Pedersen; Harald Husebye; Terje Espevik; Kirsten Sandvig
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-03
Journal Detail:
Title:  FEMS immunology and medical microbiology     Volume:  61     ISSN:  1574-695X     ISO Abbreviation:  FEMS Immunol. Med. Microbiol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9315554     Medline TA:  FEMS Immunol Med Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  63-75     Citation Subset:  IM    
Copyright Information:
© 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway.
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