GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

被引:95
作者
Fukazawa, Atsuko [1 ,2 ,3 ]
Alonso, Carmen [1 ,2 ,3 ]
Kurachi, Kiyotaka [1 ,2 ,3 ]
Gupta, Sonal [1 ,2 ,3 ]
Lesser, Cammie F. [3 ,4 ,5 ]
McCormick, Beth Ann [3 ,6 ]
Reinecker, Hans-Christian [1 ,2 ,3 ]
机构
[1] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
[4] Massachusetts Gen Hosp, Dept Microbiol & Mol Genet, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA
[6] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Boston, MA 02114 USA
关键词
D O I
10.1371/journal.ppat.1000228
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-kappa B activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappa B activation by H-Ala-Dc-gamma Glu-DAP (gamma TriDAP). GEF-H1 is essential for NF-kappa B 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.
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页数:15
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