Bacterial internalization is required to trigger NIK-dependent NF-κB activation in response to the bacterial type three secretion system
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 become internalized into host cells, induce a NIK-dependent response and nuclear entry of the non-canonical NF-κB subunit p52. Blocking actin polymerization and uptake of effector mutant bacteria using cytochalasin D shifted the host NF-κB 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-κB 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
PloS one - 12(2017), 2 vom: 16., Seite e0171406 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Duncan, Miles C [VerfasserIn] |
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| Links: |
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| Themen: |
Actins |
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| Anmerkungen: |
Date Completed 25.08.2017 Date Revised 13.12.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0171406 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM268702608 |
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| 245 | 1 | 0 | |a Bacterial internalization is required to trigger NIK-dependent NF-κB activation in response to the bacterial type three secretion system |
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| 500 | |a Date Revised 13.12.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 become internalized into host cells, induce a NIK-dependent response and nuclear entry of the non-canonical NF-κB subunit p52. Blocking actin polymerization and uptake of effector mutant bacteria using cytochalasin D shifted the host NF-κB 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-κB 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 | ||
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| 700 | 1 | |a Herrera, Natalia G |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Kevin S |e verfasserin |4 aut | |
| 700 | 1 | |a Engel, Joanne N |e verfasserin |4 aut | |
| 700 | 1 | |a Auerbuch, Victoria |e verfasserin |4 aut | |
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