Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice

Cell Reports

Andrew M. Ellisdon¹  James C. Whisstock¹  Rhoel R. Dinglasan²  Rebecca E. Tweedell²  Donna N. Douglas³  Norman M. Kneteman³  Sash Lopaticki⁴  Kelly L. Rogers⁴  Charlie Jennison⁴  Justin A. Boddey⁴  Cody C. Allison⁴  Jennifer S. Armistead⁴  Sara M. Erickson⁴  Matthew T. O’Neill⁴  Annie S.P. Yang⁴ 

[1] Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton 3800, VIC, Australia;Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;Department of Surgery, University of Alberta, Edmonton, AB T6G 2E1, Canada;Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia;

关键词: malaria;    sporozoite;    hepatocyte;    virulence;    motility;    invasion;    perforin;    SPECT;    transmission;    genetics;   

DOI  :  10.1016/j.celrep.2017.03.017

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown