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Updated: Jul 15, 2026
Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
Recombinant human IFN-alpha inhibits cerebral malaria and reduces parasite burden in mice
Ana Margarida Vigário1, Elodie Belnoue, Anne Charlotte Grüner
1Institut Cochin, Département d'Immunologie, Paris, France.
Abstract:
Most C57BL/6 mice infected i.p. with Plasmodium berghei ANKA (PbA) die between 7 and 14 days with neurologic signs, and the remainder die later (>15 days) with severe anemia. Daily i.p. injections of a recombinant human IFN-alpha (active on mouse cells) prevented death by cerebral malaria (87% deaths in the control mice vs 6% in IFN-alpha-treated mice). The mechanisms of this IFN-alpha protective effect were multiple. IFN-alpha-treated, PbA-infected mice showed 1) a marked decrease in the number of PbA parasites in the blood mediated by IFN-gamma, 2) less sequestered parasites in cerebral vessels, 3) reduced up-regulation of ICAM-1 expression in brain endothelial cells, 4) milder rise of blood levels of TNF, 5) increased levels of IFN-gamma in the blood resulting from an increased production by splenic CD8+ T cells, and 6) fewer leukocytes (especially CD8+ T cells) sequestered in cerebral vessels. On the other hand, IFN-alpha treatment did not affect the marked anemia observed in PbA-infected mice. Survival time in IFN-alpha-treated mice was further increased by performing three blood transfusions over consecutive days.
Insights
Interferon-alpha (IFN-alpha) treatment significantly reduced deaths from cerebral malaria in mice infected with Plasmodium berghei ANKA. This treatment protected against neurological symptoms and parasite sequestration in the brain.
Area of Science:
- Immunology
- Infectious Diseases
- Malariology
Background:
- Plasmodium berghei ANKA (PbA) infection in C57BL/6 mice typically leads to fatal cerebral malaria or severe anemia.
- Cerebral malaria is characterized by neurological signs and parasite sequestration in cerebral vessels.
Purpose of the Study:
- To investigate the protective effects of recombinant human interferon-alpha (IFN-alpha) against PbA-induced cerebral malaria.
- To elucidate the underlying mechanisms of IFN-alpha's protective action.
Main Methods:
- C57BL/6 mice were infected with PbA and treated with daily intraperitoneal injections of human IFN-alpha.
- Control groups received no treatment.
- Parasitemia, parasite sequestration, ICAM-1 expression, TNF levels, IFN-gamma levels, and leukocyte infiltration were assessed.
Main Results:
- IFN-alpha treatment dramatically reduced mortality from cerebral malaria (6% vs 87% in controls).
- IFN-alpha decreased blood parasitemia, cerebral parasite sequestration, ICAM-1 upregulation, and TNF levels.
- Increased IFN-gamma production by splenic CD8+ T cells and reduced leukocyte sequestration in cerebral vessels were observed.
- IFN-alpha did not impact the severity of anemia.
Conclusions:
- Human IFN-alpha provides significant protection against experimental cerebral malaria in mice.
- The protective mechanisms involve reduced parasite load, decreased neuroinflammation, and modulated immune cell responses.
- IFN-alpha is a promising therapeutic candidate for cerebral malaria, though anemia remains a challenge.
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