Imperial College London
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DrThomasClarke

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2074thomas.clarke

 
 
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Location

 

5.40DFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Clarke:2011:10.1016/j.chom.2011.04.012,
author = {Clarke, TB and Francella, N and Huegel, A and Weiser, JN},
doi = {10.1016/j.chom.2011.04.012},
journal = {Cell Host Microbe},
pages = {404--414},
title = {Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium.},
url = {http://dx.doi.org/10.1016/j.chom.2011.04.012},
volume = {9},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Streptococcus pneumoniae and Haemophilus influenzae are members of the normal human nasal microbiota with the ability to cause invasive infections. Bacterial invasion requires translocation across the epithelium; however, mechanistic understanding of this process is limited. Examining the epithelial response to murine colonization by S. pneumoniae and H. influenzae, we observed the TLR-dependent downregulation of claudins 7 and 10, tight junction components key to the maintenance of epithelial barrier integrity. When modeled in vitro, claudin downregulation was preceded by upregulation of SNAIL1, a transcriptional repressor of tight junction components, and these phenomena required p38 MAPK and TGF-β signaling. Consequently, downregulation of SNAIL1 expression inhibited bacterial translocation across the epithelium. Furthermore, disruption of epithelial barrier integrity by claudin 7 inhibition in vitro or TLR stimulation in vivo promoted bacterial translocation. These data support a general mechanism for epithelial opening exploited by invasive pathogens to facilitate movement across the epithelium to initiate disease.
AU  - Clarke,TB
AU  - Francella,N
AU  - Huegel,A
AU  - Weiser,JN
DO  - 10.1016/j.chom.2011.04.012
EP  - 414
PY  - 2011///
SP  - 404
TI  - Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium.
T2  - Cell Host Microbe
UR  - http://dx.doi.org/10.1016/j.chom.2011.04.012
UR  - https://www.ncbi.nlm.nih.gov/pubmed/21575911
VL  - 9
ER  -
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