Late Repression of NF-κB Activity by Invasive but Not Non-Invasive Meningococcal Isolates Is Required to Display Apoptosis of Epithelial Cells

PLoS Pathogens

Hela El Kafsi¹  Aziza Abaza¹  Dario Giorgini¹  Ala-Eddine Deghmane¹  Muhamed-Kheir Taha¹ 

[1] Institut Pasteur, Invasive Bacterial Infections Unit, Paris, France

关键词: Apoptosis;    Transcription factors;    Meningococcal disease;    Epithelial cells;    Infectious disease control;    Molting;    Neisseria meningitidis;    Vector-borne diseases;   

DOI  :  10.1371/journal.ppat.1002403

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 9h 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.

【 授权许可】

CC BY