Modulation of the NF-κB Pathway by Bordetella pertussis Filamentous Hemagglutinin

Background: Filamentous hemagglutinin (FHA) is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-kappa B transcription factor family in these host cell responses, we examined the effect of FHA on NF-kappa B activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection. Methodology/Principal Findings: Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-kappa B pathway, as manifested by the degradation of cytosolic I kappa B alpha, by NF-kappa B DNA binding, and by the subsequent secretion of NF-kappa B-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic I kappa B alpha, and the failure of TNF-alpha to activate NF-kappa B. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells. Conclusions: These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-kappa B activation, and perhaps lead to a compromised immune response to this bacterial pathogen.