Hyperinvasive Meningococci Induce Intra-nuclear Cleavage of the NF-κB Protein p65/RelA by Meningococcal IgA Protease

Differential modulation of nf-κb during meningococcal infection is critical in innate immune response to meningococcal disease. non-invasive isolates of neisseria meningitidis provoke a sustained nf-κb activation in epithelial cells. however,the hyperinvasive isolates of the st-11 clonal complex (st-11) only induce an early nf-κb activation followed by a sustained activation of jnk and apoptosis. we show that this temporal activation of nf-κb was caused by specific cleavage at the c-terminal region of nf-κb p65/rela component within the nucleus of infected cells. this cleavage was mediated by the secreted 150 kda meningococcal st-11 iga protease carrying nuclear localisation signals (nls) in its α-peptide moiety that allowed efficient intra-nuclear transport. in a collection of non-st-11 healthy carriage isolates lacking nls in the α-peptide,secreted iga protease was devoid of intra-nuclear transport. this part of iga polymorphism allows non-invasive isolates lacking nls,unlike hyperinvasive st-11 isolates of n. meningitides habouring nls in their α-peptide,to be carried asymptomatically in the human nasopharynx through selective eradication of their ability to induce apoptosis in infected epithelial cells. © 2015 besbes et al.