Fauconnier, M., Palomo, J., Bourigault, M. L., Meme, S., Szeremeta, F., Beloeil, J. C., Danneels, A., Charron, S., Rihet, P., Ryffel, B. and Quesniaux, V. F. J.
The Journal of Immunology 188 (4) 1905-1914
publié le , mis à jour le
A Th1 response is required for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The role of pro-Th1 IL-12 in malaria is complex and controversial. In this study, we addressed the role of IL-12R beta 2 in ECM development. C57BL/6 mice deficient for IL-12R beta 2, IL-12p40, or IL-12p35 were analyzed for ECM development after blood-stage PbA infection in terms of ischemia and blood flow by noninvasive magnetic resonance imaging and angiography, T cell recruitment, and gene expression. Without IL-12R beta 2, no neurologic sign of ECM developed upon PbA infection. Although wildtype mice developed distinct brain microvascular pathology, ECM-resistant, IL-12R beta 2-deficient mice showed unaltered cerebral microcirculation and the absence of ischemia after PbA infection. In contrast, mice deficient for IL-12p40 or IL-12p35 were sensitive to ECM development. The resistance of IL-12R beta 2-deficient mice to ECM correlated with reduced recruitment of activated T cells and impaired overexpression of lymphotoxin-alpha, TNF-alpha, and IFN-gamma in the brain after PbA infection. Therefore, IL-12R beta 2 signaling is essential for ECM development but independent from IL-12p40 and IL-12p35. We document a novel link between IL-12R beta 2 and lymphotoxin-alpha, TNF-alpha, and IFN-gamma expression, key cytokines for ECM pathogenesis.