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Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.
Sharma, Shruti; DeOliveira, Rosane B; Kalantari, Parisa; Parroche, Peggy; Goutagny, Nadege; Jiang, Zhaozhao; Chan, Jennie; Bartholomeu, Daniella C; Lauw, Fanny; Hall, J Perry; Barber, Glen N; Gazzinelli, Ricardo T; Fitzgerald, Katherine A; Golenbock, Douglas T.
Afiliación
  • Sharma S; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Immunity ; 35(2): 194-207, 2011 Aug 26.
Article en En | MEDLINE | ID: mdl-21820332
Although 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oligonucleótidos / Plasmodium falciparum / ADN Protozoario / Malaria Falciparum / Secuencia Rica en At Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oligonucleótidos / Plasmodium falciparum / ADN Protozoario / Malaria Falciparum / Secuencia Rica en At Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos