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

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.

Palomo J ，Fauconnier M ，Coquard L ，Gilles M ，Meme S ，Szeremeta F ，Fick L ，Franetich JF ，Jacobs M ，Togbe D ，Beloeil JC ，Mazier D ，Ryffel B ，Quesniaux VF ... -  《-》

IL-12Rβ2 is essential for the development of experimental cerebral malaria.

Fauconnier M ，Palomo J ，Bourigault ML ，Meme S ，Szeremeta F ，Beloeil JC ，Danneels A ，Charron S ，Rihet P ，Ryffel B ，Quesniaux VF ... -  《-》

Critical role of IL-33 receptor ST2 in experimental cerebral malaria development.

Cerebral malaria, a severe complication of Plasmodium falciparum infection, can be modeled in murine Plasmodium berghei ANKA (PbA) infection. PbA-induced experimental cerebral malaria (ECM) is CD8(+) T-cell mediated, and influenced by TH 1/TH 2 balance. Here, we show that IL-33 expression is increased in brain undergoing ECM and we address the role of the IL-33/ST2 pathway in ECM development. ST2-deficient mice were resistant to PbA-induced neuropathology. They survived >20 days with no ECM neurological sign and a preserved cerebral microcirculation, while WT mice succumbed within 10 days with ECM, brain vascular leakage, distinct microvascular pathology obstruction, and hemorrhages. Parasitemia and brain parasite load were similar in ST2-deficient and WT mice. Protection was accompanied by reduced brain sequestration of activated CD4(+) T cells and perforin(+) CD8(+) T cells. While IFN-γ and T-cell-attracting chemokines CXCL9 and CXCL10 were not affected in the absence of functional ST2 pathway, the local expression of ICAM-1, CXCR3, and LT-α, crucial for ECM development, was strongly reduced, and this may explain the diminished pathogenic T-cell recruitment and resistance to ECM. Therefore, IL-33 is induced in PbA sporozoite infection, and the pathogenic T-cell responses with local microvascular pathology are dependent on IL-33/ST2 signaling, identifying IL-33 as a new actor in ECM development.

Palomo J ，Reverchon F ，Piotet J ，Besnard AG ，Couturier-Maillard A ，Maillet I ，Tefit M ，Erard F ，Mazier D ，Ryffel B ，Quesniaux VF ... -  《-》

Control of pathogenic CD8+ T cell migration to the brain by IFN-gamma during experimental cerebral malaria.

Belnoue E ，Potter SM ，Rosa DS ，Mauduit M ，Grüner AC ，Kayibanda M ，Mitchell AJ ，Hunt NH ，Rénia L ... -  《-》

The transcription factor T-bet regulates parasitemia and promotes pathogenesis during Plasmodium berghei ANKA murine malaria.

Oakley MS ，Sahu BR ，Lotspeich-Cole L ，Solanki NR ，Majam V ，Pham PT ，Banerjee R ，Kozakai Y ，Derrick SC ，Kumar S ，Morris SL ... -  《-》