Sharma, ShrutieDeOliveira, Rosane B.Kalantari, ParisaParroche, PeggyGoutagny, NadegeJiang, ZhaozhaoChan, JennieBartholomeu, Daniella C.Lauw, Fanny N.Hall, J. PerryBarber, Glen N.Gazzinelli, Ricardo TFitzgerald, Katherine AGolenbock, Douglas T.2022-08-232022-08-232011-08-262012-05-31Immunity. 2011 Aug 26;35(2):194-207. Epub 2011 Aug 4. <a href="http://dx.doi.org/10.1016/j.immuni.2011.05.016" target="_blank">Link to article on publisher's site</a>1074-7613 (Linking)10.1016/j.immuni.2011.05.01621820332https://hdl.handle.net/20.500.14038/34912Although Toll-like receptor 9 (TLR9) has been implicated in cytokine and type I interferon (IFN) production during malaria in humans and mice, the high AT content of the Plasmodium falciparum genome prompted us to examine the possibility that malarial DNA triggered TLR9-independent pathways. Over 6000 ATTTTTAC ("AT-rich") motifs are present in the genome of P. falciparum, which we show here potently induce type I IFNs. Parasite DNA, parasitized erythrocytes and oligonucleotides containing the AT-rich motif induce type I IFNs via a pathway that did not involve the previously described sensors TLR9, DAI, RNA polymerase-III or IFI16/p204. Rather, AT-rich DNA sensing involved an unknown receptor that coupled to the STING, TBK1 and IRF3-IRF7 signaling pathway. Mice lacking IRF3, IRF7, the kinase TBK1 or the type I IFN receptor were resistant to otherwise lethal cerebral malaria. Collectively, these observations implicate AT-rich DNA sensing via STING, TBK1 and IRF3-IRF7 in P. falciparum malaria.en-USAT Rich SequenceAnimalsDNA, ProtozoanGene Expression ProfilingHumansImmunity, InnateInterferon Regulatory Factor-3Interferon Regulatory Factor-7Interferon Type IMalaria, FalciparumMembrane ProteinsMiceMice, KnockoutOligonucleotidesPlasmodium falciparumProtein-Serine-Threonine KinasesReceptor, Interferon alpha-betaSignal TransductionImmunology and Infectious DiseaseJournal Articlehttps://escholarship.umassmed.edu/infdis_pp/1382924424infdis_pp/138