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

Ala-Eddine Deghmane (1) , Hela El Kafsi (1) , Dario Giorgini (1) , Aziza Abaza (1) , Muhamed-Kheir Taha (1)

1 Infections Bactériennes Invasives

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-a 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-kB activity in infected epithelial cells. ST-11 invasive isolates initially triggered a strong NF-kB 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-kB 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.

Domains: Life Sciences [q-bio]; Human health and pathology; Infectious diseases

Ala-Eddine Deghmane, Hela El Kafsi, Dario Giorgini, Aziza Abaza, Muhamed-Kheir Taha. Late Repression of NF-κB Activity by Invasive but Not Non-Invasive Meningococcal Isolates Is Required to Display Apoptosis of Epithelial Cells.. PLoS Pathogens, 2011, 7 (12), pp.e1002403. ⟨10.1371/journal.ppat.1002403⟩. ⟨pasteur-02093130⟩