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