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Bacterial internalization is required to trigger NIK-dependent NF-?B activation in response to the bacterial type three secretion system.


ABSTRACT: Infection of human cells with Yersinia pseudotuberculosis expressing a functional type III secretion system (T3SS) leads to activation of host NF-?B. We show that the Yersinia T3SS activates distinct NF-?B pathways dependent upon bacterial subcellular localization. We found that wildtype Yersinia able to remain extracellular triggered NF-?B activation independently of the non-canonical NF-?B kinase NIK in HEK293T cells. In contrast, Yersinia lacking the actin-targeting effectors YopEHO, which become internalized into host cells, induce a NIK-dependent response and nuclear entry of the non-canonical NF-?B subunit p52. Blocking actin polymerization and uptake of effector mutant bacteria using cytochalasin D shifted the host NF-?B response from NIK-independent to primarily NIK-dependent. We observed similar results using Pseudomonas aeruginosa, which expresses a related T3SS and the actin-targeting effector ExoT. As the NF-?B response of HEK293T cells to effectorless Yersinia has been used both as a screening tool for chemical inhibitors of the T3SS and for bacterial forward genetic screens, a better understanding of this response is important for tool optimization and interpretation.

SUBMITTER: Duncan MC 

PROVIDER: S-EPMC5293232 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Bacterial internalization is required to trigger NIK-dependent NF-κB activation in response to the bacterial type three secretion system.

Duncan Miles C MC   Herrera Natalia G NG   Johnson Kevin S KS   Engel Joanne N JN   Auerbuch Victoria V  

PloS one 20170206 2


Infection of human cells with Yersinia pseudotuberculosis expressing a functional type III secretion system (T3SS) leads to activation of host NF-κB. We show that the Yersinia T3SS activates distinct NF-κB pathways dependent upon bacterial subcellular localization. We found that wildtype Yersinia able to remain extracellular triggered NF-κB activation independently of the non-canonical NF-κB kinase NIK in HEK293T cells. In contrast, Yersinia lacking the actin-targeting effectors YopEHO, which be  ...[more]

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