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Regulation of apoptosis and anti-apoptosis signalling by Francisella tularensis
- Source :
-
Microbes & Infection . Feb2010, Vol. 12 Issue 2, p126-134. 9p. - Publication Year :
- 2010
-
Abstract
- Francisella tularensis induces apoptosis within macrophages but the temporal and spatial modulation through activation of caspase-1, caspase-3, and the anti-apoptosis nuclear transcription factor B (NF-κB) is not known. Whether escape of the bacteria into the cytosol is sufficient and/or essential for activation of NF-κB is not known. Our results show that F. tularensis subsp. novicida induces sustained nuclear translocation of NF-κB at early time points after infection of human monocytes derived macrophages (hMDMs). The sustained nuclear translocation of NF-κB is defective in the iglC mutant that fails to escape into the cytosol of macrophages. Nuclear translocation of NF-κB by the wild type strain is abolished upon treatment with the NF-κB inhibitor caffein acid phenyl ester. While the wild type strain triggers caspase-3 and caspase-1 activation by 6 h post-infection the iglC mutant is defective in triggering both caspases. In hMDMs treated with the apoptosis-inducing agent, staurosporin, there is an induction of cell death in the iglC mutant-infected macrophages despite reduced frequency of caspase-1 and caspase-3 activity. The wt-infected macrophages are resistant to cell death-induced agent. We conclude that although caspase-1 and capsase-3 are triggered within F. tularensis-infected hMDMs during early stages of infection, cell death is delayed, which is correlated with simultaneous activation of NF-κB. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 12864579
- Volume :
- 12
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Microbes & Infection
- Publication Type :
- Academic Journal
- Accession number :
- 47841698
- Full Text :
- https://doi.org/10.1016/j.micinf.2009.11.003