Dynamics of transcription of immunomodulatory genes in endothelial cells infected with different coccidian parasites

Abstract

Sporozoites of Eimeria bovis and tachyzoites of Neospora caninum and Toxoplasma gondii are able to invade and to replicate in endothelial cells. Here we report on responses of bovine umbilical vein endothelial cells (BUVEC) in vitro to these coccidial infections by determining mRNA levels of the CXC chemokines GRO-α, IL-8 and IP-10, the CC chemokines MCP-1 and RANTES and of GM-CSF, COX-2 and iNOS relative to the level of housekeeping gene (GAPDH) transcription. T. gondii and N. caninum tachyzoites caused profound transcriptional upregulation of all genes in question. In general, upregulation started 2–4 h p.i. and maximum transcript levels were observed 4 h p.i. GRO-α and IL-8 gene transcription had decreased to almost control levels by 12 h p.i.; in the case of the other chemokines enhanced transcript levels persisted longer or showed a biphasic time-course. A similar time-course to CC chemokines was observed for GM-CSF mRNA, whilst COX-2 gene transcript peaks were detected at 2–4 h p.i. and 48–72 h p.i. iNOS mRNA levels increased from 4 to 48 h p.i. In contrast, E. bovis sporozoites failed to induce the transcription of CXC chemokine genes and of COX-2, and only caused moderate transcription upregulation of the other genes considered. In conclusion, infections of BUVEC with these coccidian parasites result in host cell activation associated with enhanced transcription of genes encoding for proinflammatory and immunomodulatory molecules, which are important for innate immune reactions and the transition to adaptive immunity. Differences between E. bovis versus T. gondii and N. caninum may illustrate a particular evasion strategy of E. bovis sporozoites, which is related to their need to persist in the host cell for a long period of time and to the avoidance of inflammatory process-induction.