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

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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Fukazawa A,Alonso C,Kurachi K,Gupta S,Lesser CF,McCormick BA,Reinecker HC

doi

10.1371/journal.ppat.1000228

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

e1000228

issue

11

eissn

1553-7366

issn

1553-7374

journal_volume

4

pub_type

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