title: Activation of NF-κB by Neisseria gonorrhoeae is associated with microcolony formation and type IV pilus retraction.
abstract: The early stage of infection with Neisseria gonorrhoeae (Ngo), the causative agent of gonorrhoea, is marked by type IV pilus (Tfp)-mediated attachment and the formation of bacterial microcolonies on epithelial cells. Retraction of the Ngo Tfp generates substantial force on its substrate which can elicit host cell signalling. Here, we observed that this retraction force could also activate nuclear factor (NF)-κB, the central signalling cascade of innate immunity. Using a p65-GFP-expressing epithelial cell line, we show that piliated Ngo induce asynchronous NF-κB activation in infected cells, which is temporally associated with the formation of gonococcal microcolonies. A mutant lacking PilT, an ATPase necessary for Tfp retraction, induced markedly reduced NF-κB activation. This was accompanied by decreased NF-κB target gene transcription and cytokine release. The impaired ability of the pilT mutant to activate NF-κB was compensated by applying mechanical shear stress to the infected host cells, indicating that the mechanical forces generated by retractile pili are involved in the retraction-dependent activation of NF-κB elicited by gonococcal microcolonies. Thus, our work provides evidence for an intriguing relationship between microcolony growth, pilus retraction and host cell signalling, with likely implications with regard to the course of symptomatic versus asymptomatic gonococcal infections.
authors: Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors: Manuela
authors: M
authors: Dietrich
authors: Sina
authors: S
authors: Bartfeld
authors: Rebekka
authors: R
authors: Munke
authors: Claudia
authors: C
authors: Lange
authors: Lesley A
authors: LA
authors: Ogilvie
authors: Alexandra
authors: A
authors: Friedrich
authors: Thomas F
authors: TF
authors: Meyer