Malaria continues to pose a considerable global health threat; hence, understanding the immune response to plasmodia is of utmost importance. In Nature Medicine, Guermonprez et al. describe a mast cell–dendritic cell (DC) axis associated with plasmodia infection. Infection of mice with Plasmodium chabaudi leads to release of the cytokine Flt3L from mast cells, which substantially increases the number of CD8α+ DCs and, in turn, activates CD8+ T cells. The authors trace those effects to higher expression of xanthine dehydrogenase in a yet-to-be identified radiosensitive cell population. That population responds to type I interferons produced during infection. Plasmodia-infected erythrocytes release hypoxanthine, which then can be converted to uric acid by xanthine dehydrogenase. Uric acid triggers mast cell degranulation and cleavage of membrane-tethered Flt3L. A similar response occurs in human patients with malaria, which suggests that this innate response to plasmodia is conserved.

Nat. Med. (19 May 2013) doi:10.1038/nm.3197