title: Anti-CD81 but not anti-SR-BI blocks Plasmodium falciparum liver infection in a humanized mouse model.
abstract: OBJECTIVE
  Plasmodium falciparum sporozoites, deposited in the skin by infected Anopheles mosquitoes taking a blood meal, cross the endothelium of skin capillaries and travel to the liver where they traverse Kupffer cells and hepatocytes to finally invade a small number of the latter. In hepatocytes, sporozoites replicate, differentiate and give rise to large numbers of merozoites that are released into the bloodstream where they invade red blood cells, thus initiating the symptomatic blood stage. Using in vitro systems and rodent models, it has been shown that the hepatocyte receptors CD81 and scavenger receptor type B class I (SR-BI) play a pivotal role during sporozoite invasion. We wanted to evaluate whether these two entry factors are genuine drug targets for the prevention of P. falciparum infection in humans.
  
  
  METHODS
  Immunodeficient mice of which the liver is largely repopulated by human hepatocytes were treated with monoclonal antibodies blocking either CD81 or SR-BI 1 day prior to challenge with infected mosquitoes. P. falciparum infection of the liver was demonstrated using a qPCR assay.
  
  
  RESULTS
  In human liver chimeric mice, an antibody directed against CD81 completely blocked P. falciparum sporozoite invasion while SR-BI-specific monoclonal antibodies did not influence in vivo infection.
  
  
  CONCLUSIONS
  These observations confirm the role of CD81 in liver-stage malaria and question that of SR-BI. CD81 might be a valuable drug target for the prevention of malaria.
authors: Center for Vaccinology, Ghent University, De Pintelaan 185, 9000 Gent, Belgium.
authors: Lander
authors: L
authors: Foquet
authors: Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
authors: Cornelus C
authors: CC
authors: Hermsen
authors: Center for Vaccinology, Ghent University, De Pintelaan 185, 9000 Gent, Belgium.
authors: Lieven
authors: L
authors: Verhoye
authors: Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
authors: Geert-Jan
authors: GJ
authors: van Gemert
authors: Keires AG, Elisabethenstrasse 15, 4051 Basel, Switzerland.
authors: Riccardo
authors: R
authors: Cortese
authors: CEINGE, Via Comunale Margherita, 484-538, 80131 Naples, Italy Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Corso Umberto I, 80138 Naples, Italy.
authors: Alfredo
authors: A
authors: Nicosia
authors: Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
authors: Robert W
authors: RW
authors: Sauerwein
authors: Center for Vaccinology, Ghent University, De Pintelaan 185, 9000 Gent, Belgium.
authors: Geert
authors: G
authors: Leroux-Roels
authors: Center for Vaccinology, Ghent University, De Pintelaan 185, 9000 Gent, Belgium philip.meuleman@ugent.be.
authors: Philip
authors: P
authors: Meuleman
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D018955:CD36 Antigens / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D016513:Mice, SCID; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D060225:Tetraspanin 28 / Q000037:antagonists & inhibitors*
chemical_list: D018955:CD36 Antigens; C554798:CD81 protein, human; D060225:Tetraspanin 28
keywords: CD81; P. falciparum; SR-BI; hepatocyte entry; liver stage; malaria; sporozoites