Journal article
Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice
ASP Yang, MT O'Neill, C Jennison, S Lopaticki, CC Allison, JS Armistead, SM Erickson, KL Rogers, AM Ellisdon, JC Whisstock, RE Tweedell, RR Dinglasan, DN Douglas, NM Kneteman, JA Boddey
Cell Reports | CELL PRESS | Published : 2017
Open access
Abstract
Malaria sporozoites are deposited into the skin by mosquitoes and infect hepatocytes. The molecular basis of how Plasmodium falciparum sporozoites migrate through host cells is poorly understood, and direct evidence of its importance in vivo is lacking. Here, we generated traversal-deficient sporozoites by genetic disruption of sporozoite microneme protein essential for cell traversal (PfSPECT) or perforin-like protein 1 (PfPLP1). Loss of either gene did not affect P. falciparum growth in erythrocytes, in contrast with a previous report that PfPLP1 is essential for merozoite egress. However, although traversal-deficient sporozoites could invade hepatocytes in vitro, they could not establish ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank the Melbourne Red Cross for human erythrocytes, Marcello Jacobs-Lorena for the Johns Hopkins University strain of Anopheles stephensi, the US Naval Medical Research Center for HC-04 cells, Ian Cockburn for Hepa1-6 cells, and Fidel Zavala, Alan Cowman, and Jana McBride for CSP, AMA1, and EXP2 antibodies, respectively. We sincerely thank Jelena Levitskaya, Stefanie Trop, Peter Dumoulin, Jinxia Ma, John Sacci, Jr., Julie Healer, and Melissa Hobbs for sharing technical expertise or providing valuable technical assistance, and Alan Cowman and Marc Pellegrini for stimulating discussions. This work was supported by the National Health and Medical Research Council of Australia (Project Grant 1049811), Human Frontiers Science Program (Young Investigator Grant RGY0073/2012), Ramaciotti Foundation (Establishment Grant 3197/2010), and Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. A.S.P.Y. was supported by an Australian Postgraduate Award, and J.A.B. was supported by an Australian Research Council Queen Elizabeth II Fellowship (DP110105395). The funders had no role in study design or the decision to publish.