Journal article
Targeting the Extrinsic Pathway of Hepatocyte Apoptosis Promotes Clearance of Plasmodium Liver Infection
G Ebert, S Lopaticki, MT O'Neill, RWJ Steel, M Doerflinger, P Rajasekaran, ASP Yang, S Erickson, L Ioannidis, P Arandjelovic, L Mackiewicz, C Allison, J Silke, M Pellegrini, JA Boddey
Cell Reports | CELL PRESS | Published : 2020
Abstract
Ebert et al. reveal that cellular inhibitor of apoptosis proteins (cIAPs) are upregulated in the liver during Plasmodium infection. Inactivation of cIAPs kills Plasmodium liver stages via TNF-mediated apoptosis of infected hepatocytes, affecting disease and promoting immunity. Targeting extrinsic apoptosis of infected host cells may be an antimalarial avenue.
Grants
Awarded by Human Frontier Science Program
Funding Acknowledgements
We thank the Australian Red Cross Blood Service for supplying buffy packs, Lachlan Whitehead and Charlie Jennison for valuable technical assistance, and Diana Hansen for helpful discussions. This work was supported by Australian National Health and Medical Research Council Project Grants 1049811, 1139153 (J.A.B.), 1006592, 1045549, and 1065626 (M.P.); National Health and Medical Research Council (NHMRC) Fellowships 1123727 (J.A.B.) and 1107149 (J.S.); The Sylvia & Charles Viertel Senior Medical Research Fellowship (M.P.); the Human Frontiers Science Program (Young Investigator Grant RGY0073 to J.A.B.); Australian Postgraduate Awards (P.R. and A.S.P.Y.); the Victorian State Government Operational Infrastructure Support; and the Independent Research Institutes Infrastructure Support Scheme of the Australian Government NHMRC.