Scavenger receptor BI boosts hepatocyte permissiveness to Plasmodium infection

Cell Host Microbe. 2008 Sep 11;4(3):283-92. doi: 10.1016/j.chom.2008.07.013.


Infection of hepatocytes by Plasmodium falciparum sporozoites requires the host tetraspanin CD81. CD81 is also predicted to be a coreceptor, along with scavenger receptor BI (SR-BI), for hepatitis C virus. Using SR-BI-knockout, SR-BI-hypomorphic and SR-BI-transgenic primary hepatocytes, as well as specific SR-BI-blocking antibodies, we demonstrate that SR-BI significantly boosts hepatocyte permissiveness to P. falciparum, P. yoelii, and P. berghei entry and promotes parasite development. We show that SR-BI, but not the low-density lipoprotein receptor, acts as a major cholesterol provider that enhances Plasmodium infection. SR-BI regulates the organization of CD81 at the plasma membrane, mediating an arrangement that is highly permissive to penetration by sporozoites. Concomitantly, SR-BI upregulates the expression of the liver fatty-acid carrier L-FABP, a protein implicated in Plasmodium liver-stage maturation. These findings establish the mechanistic basis of the CD81-dependent Plasmodium sporozoite invasion pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cells, Cultured
  • Cholesterol / metabolism
  • Female
  • Hepatocytes / metabolism*
  • Hepatocytes / parasitology*
  • Host-Parasite Interactions*
  • Humans
  • Liver Diseases / metabolism
  • Liver Diseases / parasitology
  • Malaria / metabolism*
  • Malaria / parasitology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmodium / physiology*
  • Scavenger Receptors, Class B / genetics
  • Scavenger Receptors, Class B / metabolism*
  • Schizonts / physiology
  • Sporozoites / physiology
  • Tetraspanin 28


  • Antigens, CD
  • CD81 protein, human
  • Cd81 protein, mouse
  • Scavenger Receptors, Class B
  • Tetraspanin 28
  • Cholesterol