Administration of Agaricus blazei modulated cytokine expression in the spleen and brain and protected against CM development. C57BL/6 mice were pre-treated with 100 mg/kg of A. blazei extract, Fraction C (100 or 800 mg/kg) or chloroquine (30 mg/kg) 3 days before infection, then infected with 105 parasitized RBCs IP via, and treated until 5 dpi. Production of IL-12, IFN-γ, TNF, IL-6, IL-1β, IL-17, IL-10 and TGF-β in the spleen (a) and in the brain (b) in response to infection with P. berghei, measured at 5 dpi. Cytokines expression was normalized relative to that of uninfected controls for each mouse group. c Representative histological (H&E) stained of cerebral cortex of mice, demonstrating severity of cerebral pathology on 5 dpi. It is observed cerebral cortex with normal histological aspect, containing healthy neurons in mice-uninfected and with extensive hemorrhagic area (arrow), surrounded by hyperchromatic and condensed neurons (asterisks) in P. berghei-infected animal. Small haemorrhagic focus (arrow) was detected in the brain of mice treated with chloroquine and cerebral parenchyma with normal histological aspect in mice treated with AbM aqueous extract or fraction C. Original magnification ×20. Values are expressed as mean ± SD of 5 mice per group. *p < 0.05, **p < 0.01 and ***p < 0.001 compared to P. berghei-infected mice, ANOVA followed Bonferroni’s test.