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

Publication date: 28 March 2017
Source:Cell Reports, Volume 18, Issue 13
Author(s): 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
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.

Graphical abstract

Teaser

Malaria sporozoites deposited by a mosquito into the skin must navigate to the liver and infect hepatocytes. Yang et al. reveal the importance of sporozoite transmigration through host cells to establish liver infection in humanized mice by the most virulent human malaria parasite Plasmodium falciparum.


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