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Palomo J., Fauconnier M., Coquard L., Gilles M., Meme S., Szeremeta F., Fick L., Franetich J.F., Jacobs M., Togbe D., Beloeil J.C., Mazier D., Ryffel B. and Quesniaux V.F.

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

European Journal of Immunology 43 (10) 2683-2695 - doi : 10.1002/eji.201343327

par Frapart - publié le

Abstract :

Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-gamma are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-alpha/beta in ECM development remains unclear. Here, we address the role of the IFN-alpha/beta 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-gammaR1(-)/(-) mice were fully resistant, IFNAR1(-)/(-) mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN-gammaR1(-)/(-) 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-gamma, IL-12Rbeta2, and T-cell-attracting chemokines CXCL9 and CXCL10 in IFNAR1(-)/(-) mice, more so in the absence of IFN-gammaR1. Therefore, the type I IFN-alpha/beta receptor pathway contributes to brain T-cell responses and microvascular pathology, although it is not as essential as IFN-gamma for the development of cerebral malaria upon hepatic or blood-stage PbA infection.