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) (which cross-reacts with murine cells) on C57BL/6 mice infected with Plasmodium yoelii sporozoites or parasitized erythrocytes was determined. IFN-alpha did not inhibit the development of the parasite in the liver, but it did reduce the blood parasite load and the hepatosplenomegaly induced by the infection in mice injected with blood-stage parasites. The extent of anemia in IFN-alpha-treated and control mice was similar, despite the lower parasite load in the IFN-alpha-treated mice. The reduced blood parasite load in IFN-alpha-treated mice was associated with reduced erythropoiesis and reticulocytosis. As reticulocytes are the preferred target cells for the strain of P yoelii used (P yoelii yoelii 265 BY), it was postulated that the inhibition of reticulocytosis in IFN-alpha-treated mice was causally related to the observed decreased blood parasite load. This was supported by the finding that IFN-alpha inhibited a different strain of P yoelii (17X clone A), which also displays a tropism for reticulocytes, but not a line of Plasmodium vinckei petteri, which infects only mature red blood cells. As human malaria species also display different tropism for reticulocytes, these findings could be relevant for people coinfected with multiple Plasmodium species or strains or coinfected with Plasmodium and virus. (Blood. 2001;97:3966-3971)
Vigário
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AM
INSERM Unité 445, ICGM, Université René Descartes, Hôpital Cochin, Bâtiment Gustave Roussy, 27, rue du Fbg Saint Jacques, 75014 Paris, France.
Belnoue
E
E
Cumano
A
A
Marussig
M
M
Miltgen
F
F
Landau
I
I
Mazier
D
D
Gresser
I
I
Rénia
L
L
D000818:Animals; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D008107:Liver Diseases / Q000188:drug therapy / Q000469:parasitology; D008288:Malaria / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000188:drug therapy; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000254:growth & development; D011994:Recombinant Proteins / Q000494:pharmacology; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects* / Q000469:parasitology; D013163:Splenomegaly / Q000188:drug therapy / Q000469:parasitology
D016898:Interferon-alpha; D011994:Recombinant Proteins