Bordetella pertussis filamentous hemagglutinin induces nuclear translocation of RelB/p52 in U-937 macrophages (135.24)

Abstract

Abstract Filamentous hemagglutinin (FHA) is a dominant adhesin expressed by the respiratory pathogen Bordetella pertussis that also triggers inflammatory as well as immunosuppressive functions in the host. Given the role of NF-κB transcription factor family members in these functions, we examined the effects of FHA on NF-κB activation at early and late time points in two cell types relevant to natural infection: human bronchial epithelial (BEAS-2B) cells and human macrophage-like (U-937 derived) cells. We recently showed that FHA blocks proteasomal activity in both, the bronchial epithelial cell line and in monocyte-derived macrophages, resulting in accumulation of IκBα at 2 hours or greater incubation times. RelB and alternative NF-κB pathways regulate monopoiesis and monocyte-derived dendritic cell subset development. We report here that incubation of U-937 cells with FHA for more than 4 hours results in reduced levels of cytosolic RelB and increased levels of nuclear RelB and p52, as shown by Western blot analysis. No such effects were observed in bronchial epithelial cells (BEAS-2B). These data suggest that FHA induces nuclear translocation of RelB /p52 and activation of the alternative NF-κB pathway in U-937 cells, but not in BEAS-2B cells, and offer a molecular mechanism by which FHA might affect development and maturation of myeloid host cells.