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The apicomplexan parasite  Toxoplasma gondii  produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite  Plasmodium  spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in  P .  berghei  ANKA and  T .  gondii  cell lysates. However, addition of salicylic acid to  P .  falciparum  and  T .  gondii  culture had no effect. We transfected  P .  falciparum  3D7 with the  nahG  gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting  Pseudomonas  sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E 2 , which potentially modulates host immunity as an adaptive evolution of  Plasmodium  spp. To investigate the function of salicylic acid and prostaglandin E 2  on host immunity, we established  P .  berghei  ANKA mutants expressing  nahG . C57BL/6 mice infected with  nahG  transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The  nahG -transfectant also significantly increased the mortality rate of mice. Prostaglandin E 2  reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the  nahG  transfectant. Thus, salicylic acid of  Plasmodium  spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E 2 .

Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome