Immunology

Deadly Interfer(on)ence in Malaria

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Science  23 Sep 2011:
Vol. 333, Issue 6050, pp. 1680
DOI: 10.1126/science.333.6050.1680-d
CREDIT: NIBSC/SCIENCE PHOTO LIBRARY

Malaria is a devastating disease that infects more than 250 million people worldwide, and in a small percentage of individuals, many of whom are children, the infection can progress to life-threatening cerebral malaria. The host response to Plasmodium falciparum, the parasite that causes cerebral malaria, is thought to contribute to disease pathogenesis. In order to better understand this phenomenon, Sharma et al. performed global gene expression profiling and found that type I interferons, which are cytokines typically associated with antiviral immunity, were enriched in cells isolated from febrile patients with malaria. Further analysis demonstrated that AT-rich regions of the P. falciparum genome, which number over 6000, induced type I interferon production by human cells. Surprisingly, none of the known nucleic acid sensors of the host immune system were required for parasite-induced type I interferon production. This response, however, did depend on STING and TBK1, proteins known to signal downstream other DNA sensors. Because type I interferons can cause immune pathology, the role of the STING-TBK1-type I interferon pathway was examined in a mouse model of cerebral malaria. Genetic ablation of this pathway in mice resulted in protection from disease. Whether this pathway is also an important driver of cerebral malaria in humans will need to be examined.

Immunity 35, 194 (2011).

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