Public Health - Molecular Microbiology & Immunology
Inhibition of plasmepsin activity in the liver stage of malaria infection.
Though expression of parasites-specific aspartic proteases, plasmepsins, was documented in the liver stage of malaria infection several years ago, the function of these enzymes produced by the parasite in hepatocytes remains elusive. At the same time, well established function of plasmepsins in the erythrocytic stage malaria infection, namely, their haemoglobin-degrading activity, prompted development of plasmepsin inhibitors as a novel class of anti-malarial drugs. We have recently found that MHC class I antigen presentation is altered in human hepatocytes infected with malaria. It is also known that the activity and composition of proteolytic machinery in the infected host cell can modify presentation of pathogen-derived antigens. We intend to test a hypothesis that activity of malarial plasmepsins may interfere with the MHC class processing pathway in the infected hepatocyte. Using novel inhibitors of plasmepsins, we intend to investigate the role of these proteases in the interaction of sporozoites with human liver cells with focus on the antigen presentation in the liver stage of malaria infection.
Ernesto Freire, PhD; Arts & Sciences, Biology Yuko Kawasaki, PhD; Arts & Sciences, Biology