| This is the first comprehensive investigation of the impact of Plasmodium knowlesi infection on the transcriptome of the peripheral blood mononuclear cells of rhesus macaques. The transcriptome was evaluated at six time points: before infection (the controls), the 4 th day following infection (the liver stage), the 7th, 9th, and 11th days following infection (the blood stage), and four months after curative treatment. The focus of the investigation centered on the evaluation of the innate and acquired immune responses and apoptotic pathways, and the identification of other cellular components which act to limit the progression of the infection. This comprehensive analysis provided important new information regarding host responses utilizing the P. knowlesi-rhesus macaque model. This study provided evidence for a parasite density threshold mechanism associated with the pattern recognition receptors: CD 14 and Toll-like receptors 1, 4, 6, and 8. It was also apparent that apoptosis had a prominent role in defense as indicated by up-regulated components within three different apoptotic pathways: FasL, MAP Kinase and TRAIL. Through this investigation, it was shown that gene expression associated with the defense against malaria does not always increase with the number of days of infection and that many gene expression levels which were significantly up-regulated in the earlier stages of infection decrease to the pre-infection levels as the parasite density increases. |
