CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo

Infect Immun. 2016 Jun 23;84(7):2002-2011. doi: 10.1128/IAI.01426-15. Print 2016 Jul.


CD47 engagement by the macrophage signal regulatory protein alpha (SIRPα) inhibits phagocytic activity and protects red blood cells (RBCs) from erythrophagocytosis. The role of CD47-SIRPα in the innate immune response to Plasmodium falciparum infection is unknown. We hypothesized that disruption of SIRPα signaling may enhance macrophage uptake of malaria parasite-infected RBCs. To test this hypothesis, we examined in vivo clearance in CD47-deficient mice infected with Plasmodium berghei ANKA and in vitro phagocytosis of P. falciparum-infected RBCs by macrophages from SHP-1-deficient (Shp-1(-/-)) mice and NOD.NOR-Idd13.Prkdc(scid) (NS-Idd13) mice, as well as human macrophages, following disruption of CD47-SIRPα interactions with anti-SIRPα antibodies or recombinant SIRPα-Fc fusion protein. Compared to their wild-type counterparts, Cd47(-/-) mice displayed significantly lower parasitemia, decreased endothelial activation, and enhanced survival. Using macrophages from SHP-1-deficient mice or from NS-Idd13 mice, which express a SIRPα variant that does not bind human CD47, we showed that altered SIRPα signaling resulted in enhanced phagocytosis of P. falciparum-infected RBCs. Moreover, disrupting CD47-SIRPα engagement using anti-SIRPα antibodies or SIRPα-Fc fusion protein also increased phagocytosis of P. falciparum-infected RBCs. These results indicate an important role for CD47-SIRPα interactions in innate control of malaria and suggest novel targets for intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD47 Antigen / metabolism*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Erythrocytes / parasitology
  • Host-Parasite Interactions
  • Immunity, Innate
  • Macrophages / parasitology*
  • Macrophages / physiology*
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / metabolism*
  • Malaria, Falciparum / parasitology*
  • Mice
  • Mice, Knockout
  • Phagocytosis / immunology
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / immunology*
  • Protein Binding
  • Receptors, Immunologic / metabolism*
  • Signal Transduction


  • CD47 Antigen
  • Cytokines
  • Ptpns1 protein, mouse
  • Receptors, Immunologic