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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)3105-3116
Number of pages12
JournalCell Reports
Volume18
Issue number13
DOIs
Publication statusPublished - 28 Mar 2017

Keywords

  • genetics
  • hepatocyte
  • invasion
  • malaria
  • motility
  • perforin
  • SPECT
  • sporozoite
  • transmission
  • virulence

Cite this

Yang, A. S. P., O'Neill, M. T., Jennison, C., Lopaticki, S., Allison, C. C., Armistead, J. S., ... Boddey, J. A. (2017). Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice. Cell Reports, 18(13), 3105-3116. https://doi.org/10.1016/j.celrep.2017.03.017
Yang, Annie S.P. ; O'Neill, Matthew T. ; Jennison, Charlie ; Lopaticki, Sash ; Allison, Cody C. ; Armistead, Jennifer S. ; Erickson, Sara M. ; Rogers, Kelly L. ; Ellisdon, Andrew M. ; Whisstock, James C. ; Tweedell, Rebecca E. ; Dinglasan, Rhoel R. ; Douglas, Donna N. ; Kneteman, Norman M. ; Boddey, Justin A. / Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice. In: Cell Reports. 2017 ; Vol. 18, No. 13. pp. 3105-3116.
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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.",
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Yang, ASP, 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 2017, 'Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice' Cell Reports, vol. 18, no. 13, pp. 3105-3116. https://doi.org/10.1016/j.celrep.2017.03.017

Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice. / Yang, Annie S.P.; O'Neill, Matthew T.; Jennison, Charlie; Lopaticki, Sash; Allison, Cody C.; Armistead, Jennifer S.; Erickson, Sara M.; Rogers, Kelly L.; Ellisdon, Andrew M.; Whisstock, James C.; Tweedell, Rebecca E.; Dinglasan, Rhoel R.; Douglas, Donna N.; Kneteman, Norman M.; Boddey, Justin A.

In: Cell Reports, Vol. 18, No. 13, 28.03.2017, p. 3105-3116.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice

AU - Yang, Annie S.P.

AU - O'Neill, Matthew T.

AU - Jennison, Charlie

AU - Lopaticki, Sash

AU - Allison, Cody C.

AU - Armistead, Jennifer S.

AU - Erickson, Sara M.

AU - Rogers, Kelly L.

AU - Ellisdon, Andrew M.

AU - Whisstock, James C.

AU - Tweedell, Rebecca E.

AU - Dinglasan, Rhoel R.

AU - Douglas, Donna N.

AU - Kneteman, Norman M.

AU - Boddey, Justin A.

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Y1 - 2017/3/28

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AB - 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.

KW - genetics

KW - hepatocyte

KW - invasion

KW - malaria

KW - motility

KW - perforin

KW - SPECT

KW - sporozoite

KW - transmission

KW - virulence

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U2 - 10.1016/j.celrep.2017.03.017

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Yang ASP, O'Neill MT, Jennison C, Lopaticki S, Allison CC, Armistead JS et al. Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice. Cell Reports. 2017 Mar 28;18(13):3105-3116. https://doi.org/10.1016/j.celrep.2017.03.017