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PLoS One. 2008;3(11):e3825. doi: 10.1371/journal.pone.0003825. Epub 2008 Nov 27.

Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.

Author information

1
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.

Abstract

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-kappaB transcription factor family in these host cell responses, we examined the effect of FHA on NF-kappaB 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-kappaB pathway, as manifested by the degradation of cytosolic IkappaB alpha, by NF-kappaB DNA binding, and by the subsequent secretion of NF-kappaB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IkappaB alpha, and the failure of TNF-alpha to activate NF-kappaB. 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-kappaB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.

PMID:
19043589
PMCID:
PMC2584786
DOI:
10.1371/journal.pone.0003825
[Indexed for MEDLINE]
Free PMC Article

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