Cell traversal activity is important for Plasmodium falciparum liver infection in humanized mice

Yang, AS; O&#39;Neill, MT; Jennison, C; Lopaticki, S; Allison, CC; Armistead, JS; Erickson, SM; Rogers, KL; Ellisdon, AM; Whisstock, JC; Tweedell, RE; Dinglasan, RR; Douglas, DN; Kneteman, NM; Boddey, JA

Author(s): Yang, AS; O'Neill, MT; Jennison, C; Lopaticki, S; Allison, CC; Armistead, JS; Erickson, SM; Rogers, KL; Ellisdon, AM; Whisstock, JC; Tweedell, RE; Dinglasan, RR; Douglas, DN; Kneteman, NM; Boddey, JA;
Details: Publication Year 2017-03-28,Volume 18,Issue #13,Page 3105-3116
Journal Title: Cell Reports
Publication Type: Journal Article
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 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.
Publisher: Cell Press
Research Division(s): Infection And Immunity; Systems Biology And Personalised Medicine
PubMed ID: 28355563
Publisher's Version: https://doi.org/10.1016/j.celrep.2017.03.017
Open Access at Publisher's Site: http://www.sciencedirect.com1/science/article/pii/S2211124717303340
NHMRC Grants: NHMRC/1049811,
ARC Grants: ARC/DP110105395,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-04-12 10:42:29

Last Modified: 2017-04-12 12:13:54