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The crucial role of hepatocyte growth factor receptor during liver-stage infection is not conserved among Plasmodium species

Nature Medicine volume 17, pages 1180–1181 (2011)Cite this article

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Protozoan parasites of the genus Plasmodium are the vector-borne causative agents of malaria, responsible for more than 350 million clinical cases and one million deaths annually. Studies using rodent malaria models have shown that during the bite of an infected Anopheles mosquito, Plasmodium sporozoites are transmitted and subsequently traverse a variety of cell types, wounding their membranes on the way1. This allows sporozoites to travel through the dermis into the bloodstream and then pass through the cell layer that lines blood vessels in the liver as well as several hepatocytes before taking up residence in host hepatocytes for further development as exoerythrocytic forms (EEFs)2. Although cell traversal provides a means to cross tissue barriers, it is unclear whether this constitutes its only biological role. A novel function for parasite host cell traversal was proposed by Carrolo et al.3, who showed that cell traversal by sporozoites of the rodent malaria parasite Plasmodium berghei induces secretion of hepatocyte growth factor (HGF). HGF is a soluble factor that activates the receptor tyrosine kinase MET, which is capable of initiating a cascade of signaling events that result in hepatocyte proliferation and survival. Carrolo et al.3 further showed that this signaling cascade is crucial to promote early development of EEFs and thus substantially contributes to transmission success. More recently, the same group demonstrated, again using P. berghei, that MET signaling events are important for the parasite to protect itself from host hepatocyte apoptosis4 and subsequently showed that a dietary supplement, genistein, which inhibits MET activation, can treat liver-stage malaria infection5. A fundamental question, then, is whether this unique function for cell traversal is broadly conserved among Plasmodium species and whether it is found in human malaria parasites.

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Figure 1: MET signaling is crucial for P. berghei (Pb) but not P. yoelii (Py) or P. falciparum (Pf) hepatocyte infection.

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Authors and Affiliations

  1. Seattle Biomedical Research Institute, Seattle, Washington, USA

    Alexis Kaushansky & Stefan H I Kappe

  2. Department of Global Health, University of Washington, Seattle, Washington, USA

    Stefan H I Kappe

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  1. Alexis Kaushansky
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  2. Stefan H I Kappe
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Correspondence to Stefan H I Kappe.

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Kaushansky, A., Kappe, S. The crucial role of hepatocyte growth factor receptor during liver-stage infection is not conserved among Plasmodium species. Nat Med 17, 1180–1181 (2011). https://doi.org/10.1038/nm.2456

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