Malaria is characterized by cyclical fevers and high levels of inflammation, and 
while an early inflammatory response contributes to parasite clearance, 
excessive and persistent inflammation can lead to severe forms of the disease. 
Here, we show that Plasmodium falciparum-infected erythrocytes contain uric acid 
precipitates in the cytoplasm of the parasitophorous vacuole, which are released 
when erythrocytes rupture. Uric acid precipitates are highly inflammatory 
molecules that are considered a danger signal for innate immunity and are the 
causative agent in gout. We determined that P. falciparum-derived uric acid 
precipitates induce maturation of human dendritic cells, increasing the 
expression of cell surface co-stimulatory molecules such as CD80 and CD86, while 
decreasing human leukocyte antigen-DR expression. In accordance with this, uric 
acid accounts for a significant proportion of the total stimulatory activity 
induced by parasite-infected erythrocytes. Moreover, the identification of uric 
acid precipitates in P. falciparum- and P. vivax-infected erythrocytes obtained 
directly from malaria patients underscores the in vivo and clinical relevance of 
our findings. Altogether, our data implicate uric acid precipitates as a 
potentially important contributor to the innate immune response to Plasmodium 
infection and may provide a novel target for adjunct therapies.