Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS Pathog. 2008 Nov;4(11):e1000228. doi: 10.1371/journal.ppat.1000228. Epub 2008 Nov 28.

GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors.

Author information

  • 1Department of Medicine, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-kappaB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappaB activation by H-Ala-D-gammaGlu-DAP (gammaTriDAP). GEF-H1 is essential for NF-kappaB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens.

PMID:
19043560
[PubMed - indexed for MEDLINE]
PMCID:
PMC2583055
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk