10.3389/fmicb.2019.00127.s002
Rebecca E. Tweedell
Rebecca E.
Tweedell
Dingyin Tao
Dingyin
Tao
Timothy Hamerly
Timothy
Hamerly
Tanisha M. Robinson
Tanisha M.
Robinson
Simon Larsen
Simon
Larsen
Alexander G. B. Grønning
Alexander G. B.
Grønning
Alessandra M. Norris
Alessandra M.
Norris
Jonas G. King
Jonas
G. King
Henry Chun Hin Law
Henry Chun Hin
Law
Jan Baumbach
Jan
Baumbach
Elke S. Bergmann-Leitner
Elke
S. Bergmann-Leitner
Rhoel R. Dinglasan
Rhoel R.
Dinglasan
Table_1_The Selection of a Hepatocyte Cell Line Susceptible to Plasmodium falciparum Sporozoite Invasion That Is Associated With Expression of Glypican-3.XLSX
Frontiers
2019
malaria
Plasmodium falciparum
liver stage
in vitro model
omics
glypican-3
hepatocyte
2019-02-28 04:12:22
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_1_The_Selection_of_a_Hepatocyte_Cell_Line_Susceptible_to_Plasmodium_falciparum_Sporozoite_Invasion_That_Is_Associated_With_Expression_of_Glypican-3_XLSX/7781360
<p>In vitro studies of liver stage (LS) development of the human malaria parasite Plasmodium falciparum are technically challenging; therefore, fundamental questions about hepatocyte receptors for invasion that can be targeted to prevent infection remain unanswered. To identify novel receptors and to further understand human hepatocyte susceptibility to P. falciparum sporozoite invasion, we created an optimized in vitro system by mimicking in vivo liver conditions and using the subcloned HC-04.J7 cell line that supports mean infection rates of 3–5% and early development of P. falciparum exoerythrocytic forms—a 3- to 5-fold improvement on current in vitro hepatocarcinoma models for P. falciparum invasion. We juxtaposed this invasion-susceptible cell line with an invasion-resistant cell line (HepG2) and performed comparative proteomics and RNA-seq analyses to identify host cell surface molecules and pathways important for sporozoite invasion of host cells. We identified and investigated a hepatocyte cell surface heparan sulfate proteoglycan, glypican-3, as a putative mediator of sporozoite invasion. We also noted the involvement of pathways that implicate the importance of the metabolic state of the hepatocyte in supporting LS development. Our study highlights important features of hepatocyte biology, and specifically the potential role of glypican-3, in mediating P. falciparum sporozoite invasion. Additionally, it establishes a simple in vitro system to study the LS with improved invasion efficiency. This work paves the way for the greater malaria and liver biology communities to explore fundamental questions of hepatocyte-pathogen interactions and extend the system to other human malaria parasite species, like P. vivax.</p>