In vitro Bartonella quintana infection modulates the programmed cell death and inflammatory reaction of endothelial cells.

Bartonella quintana is an epicellular bacterium, which in vivo as well as in vitro, invades endothelial cells and develops within them inducing proliferative effects that play a pivotal role in neovascular manifestation of this disease. We investigated the effect of live Bartonella quintana and its LPS on apoptosis and inflammatory response in HUVEC-C, an endothelial cell line. The kinetics of the programmed cell death of Bartonella quintana-infected HUVEC-C showed a peculiar course. Even if early during infection apoptosis reached a peak after 6 h, later on apoptosis was inhibited. Such apoptosis inhibition was not observed during Bartonella quintana lipopolysaccharide treatment because LPS-stimulated HUVEC-C did progress to cell death. Evaluation of multiple cell signal transduction pathways revealed an overexpression of Apaf 1 and caspase 8 in HUVEC-C after 2 h of infection, and of bcl-2 starting from 10 h post Bartonella quintana infection. Moreover, Bartonella quintana and its LPS showed a different effect on the activation of genes involved in inflammatory response as revealed by molecular analysis of host cells. Bartonella quintana appears to be able to inhibit programmed cell death, inducing intracellular signals leading to survival and proliferation through the bcl-2 gene, despite the early increase of inflammatory status induced in endothelial cells. This mechanism, together with a poor endotoxin ability to stimulate strong inflammatory response, could contribute to the capability of the bacteria to persist intracellularly, causing chronic disease and producing neovascular manifestations.