Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice
Annie S.P. Yang,
Matthew T. O’Neill,
Charlie Jennison,
Sash Lopaticki,
Cody C. Allison,
Jennifer S. Armistead,
Sara M. Erickson,
Kelly L. Rogers,
Andrew M. Ellisdon,
James C. Whisstock,
Rebecca E. Tweedell,
Rhoel R. Dinglasan,
Donna N. Douglas,
Norman M. Kneteman,
Justin A. Boddey
Affiliations
Annie S.P. Yang
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Matthew T. O’Neill
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Charlie Jennison
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Sash Lopaticki
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Cody C. Allison
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Jennifer S. Armistead
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Sara M. Erickson
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Kelly L. Rogers
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
Andrew M. Ellisdon
Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton 3800, VIC, Australia
James C. Whisstock
Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton 3800, VIC, Australia
Rebecca E. Tweedell
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Rhoel R. Dinglasan
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Donna N. Douglas
Department of Surgery, University of Alberta, Edmonton, AB T6G 2E1, Canada
Norman M. Kneteman
Department of Surgery, University of Alberta, Edmonton, AB T6G 2E1, Canada
Justin A. Boddey
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia
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 normal liver infection in humanized mice. This is in contrast with NF54 sporozoites, which infected the humanized mice and developed into exoerythrocytic forms. This study demonstrates that SPECT and perforin-like protein 1 (PLP1) are critical for transcellular migration by P. falciparum sporozoites and demonstrates the importance of cell traversal for liver infection by this human pathogen.
