Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA

Eur J Immunol. 2013 Oct;43(10):2683-95. doi: 10.1002/eji.201343327. Epub 2013 Jul 19.


Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-γ are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-α/β in ECM development remains unclear. Here, we address the role of the IFN-α/β pathway in ECM devel-opment in response to hepatic or blood-stage PbA infection, using mice deficient for types I or II IFN receptors. While IFN-γR1⁻/⁻ mice were fully resistant, IFNAR1⁻/⁻ mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN-γR1⁻/⁻ mice correlated with unaltered cerebral microcirculation and absence of ischemia, while WT and IFNAR1⁻/⁻ mice developed distinct microvascular pathologies. ECM resistance appeared to be independent of parasitemia. Instead, key mediators of ECM were attenuated in the absence of IFNAR1, including PbA-induced brain sequestration of CXCR3⁺-activated CD8⁺ T cells. This was associated with reduced expression of Granzyme B, IFN-γ, IL-12Rβ2, and T-cell-attracting chemokines CXCL9 and CXCL10 in IFNAR1⁻/⁻ mice, more so in the absence of IFN-γR1. Therefore, the type I IFN-α/β receptor pathway contributes to brain T-cell responses and microvascular pathology, although it is not as essential as IFN-γ for the development of cerebral malaria upon hepatic or blood-stage PbA infection.

Keywords: Chemokines; Experimental cerebral malaria; Merozoites; Sporozoites; Type I interferons (IFNs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / parasitology
  • Cell Movement / genetics
  • Cerebellum / immunology*
  • Cerebellum / parasitology
  • Cytotoxicity, Immunologic / genetics
  • Disease Progression
  • Humans
  • Interferon Type I / immunology*
  • Ischemia / genetics
  • Malaria, Cerebral / immunology*
  • Malaria, Cerebral / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microcirculation / genetics
  • Models, Animal
  • Plasmodium berghei / immunology*
  • Plasmodium falciparum / immunology*
  • Receptors, CXCR3 / metabolism
  • Receptors, Interferon / genetics
  • Sporozoites / immunology


  • Interferon Type I
  • Receptors, CXCR3
  • Receptors, Interferon