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Thromb Haemost. 2005 Aug;94(2):347-61.

The transcriptional response of human endothelial cells to infection with Bartonella henselae is dominated by genes controlling innate immune responses, cell cycle, and vascular remodelling.

Author information

1
Division of Molecular Microbiology, Biozentrum, University of Basel, Switzerland. michaela dehio@unibas.ch

Abstract

The bacterial pathogen Bartonella henselae (Bh) is responsible for a broad range of clinical manifestations, including the formation of vascular tumours as the result of pathogen-triggered vasoproliferation. In vitro, the interaction of Bh with human umbilical vein endothelial cells (Huvec) involves (i) cytoskeletal rearrangements in conjunction with bacterial internalization, (ii) nuclear factor kappaB (NFkappaB)-dependent proinflammatory activation, (iii) the inhibition of apoptosis, and (iv) the modulation of angiogenic properties such as proliferation, migration, and tubular differentiation. To study the transcriptional signature of these pathogen-triggered changes of Huvec, we performed transcriptional profiling with Affymetrix U133 GeneChips. At 6 h or 30 h of infection, a total of 706 genes displayed a clear and statistically significant change of expression (>2.5-fold, t-test p-value<0.05). These included 314 up-regulated genes dominated by the innate immune response. The gene list comprises subsets of tumour necrosis factor alpha (TNFalpha, 99 genes) and interferon alpha (IFNalpha, 30 genes) inducible genes, which encode components of the NF-kappaB-dependent proinflammatory response and the type I IFN-dependent anti-infective response, respectively. The remaining set of 197 up-regulated genes mirrors other cellular changes induced by Bh, in particular proliferation and proangiogenic activation. The set of 362 down-regulated genes includes 41TNFalpha - or IFNalpha-suppressible genes, and 52 genes involved in cell cycle control or progression. This comprehensive analysis of Bh-triggered changes of the Huvec transcriptome identified candidate genes putatively involved in controlling innate immune responses, cell cycle, and vascular remodelling, and may thus provide the basis for functional studies of the molecular mechanisms underlying these pathogen-induced cellular processes.

PMID:
16113825
DOI:
10.1160/TH05-02-0106
[Indexed for MEDLINE]

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