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 Pathogjournal_title
PLoS pathogensauthors
Fukazawa A,Alonso C,Kurachi K,Gupta S,Lesser CF,McCormick BA,Reinecker HCdoi
10.1371/journal.ppat.1000228subject
Has Abstractpub_date
2008-11-01 00:00:00pages
e1000228issue
11eissn
1553-7366issn
1553-7374journal_volume
4pub_type
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