Late repression of NF-κB activity by invasive but not non-invasive meningococcal isolates is required to display apoptosis of epithelial cells.
Meningococcal invasive isolates of the ST-11 clonal complex are most frequently associated with disease and rarely found in carriers. Unlike carriage isolates, invasive isolates induce apoptosis in epithelial cells through the TNF-α signaling pathway. While invasive and non-invasive isolates are bot...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-12-01
|
| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3228807?pdf=render |
| Summary: | Meningococcal invasive isolates of the ST-11 clonal complex are most frequently associated with disease and rarely found in carriers. Unlike carriage isolates, invasive isolates induce apoptosis in epithelial cells through the TNF-α signaling pathway. While invasive and non-invasive isolates are both able to trigger the TLR4/MyD88 pathway in lipooligosaccharide (LOS)-dependant manner, we show that only non-invasive isolates were able to induce sustained NF-κB activity in infected epithelial cells. ST-11 invasive isolates initially triggered a strong NF-κB activity in infected epithelial cells that was abolished after 9 h of infection and was associated with sustained activation of JNK, increased levels of membrane TNFR1, and induction of apoptosis. In contrast, infection with carriage isolates lead to prolonged activation of NF-κB that was associated with a transient activation of JNK increased TACE/ADAM17-mediated shedding of TNFR1 and protection against apoptosis. Our data provide insights to understand the meningococcal duality between invasiveness and asymptomatic carriage. |
|---|---|
| ISSN: | 1553-7366 1553-7374 |