Inhibition of Plasmodium yoelii blood-stage malaria by interferon alpha through the inhibition of the production of its target cell, the reticulocyte

The effect of a recombinant hybrid human interferon alpha (IFN-alpha) (whic h cross-reacts with murine cells) on C57BL/6 mice infected with Plasmodium yoelii sporozoites or parasitized erythrocytes was determined. IFN-alpha di d not inhibit the development of the parasite in the liver, but it did redu ce the blood parasite load and the hepatosplenomegaly induced by the infect ion in mice injected with blood-stage parasites. The extent of anemia in IF N-alpha -treated and control mice was similar, despite the lower parasite l oad in the IFN-alpha -treated mice. The reduced blood parasite load in IFN- alpha -treated mice was associated with reduced erythropoiesis and reticulo cytosis. As reticulocytes are the preferred target cells for the strain of P yoelii used (P yoelii yoelii 265 BY), it was postulated that the inhibiti on of reticulocytosis in IFN-alpha -treated mice was causally related to th e observed decreased blood parasite load. This was supported by the finding that IFN-alpha inhibited a different strain of P yoelii(17X clone A), whic h also displays a tropism for reticulocytes, but not a line of Plasmodium v inckei petteri, which infects only mature red blood cells. As human malaria species also display different tropism for reticulocytes, these findings c ould be relevant for people coinfected with multiple Plasmodium species or strains or coinfected with Plasmodium and virus.