Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome

Shruti Sharma, Rosane B. DeOliveira, Parisa Kalantari, Peggy Parroche, Nadege Goutagny, Zhaozhao Jiang, Jennie Chan, Daniella C. Bartholomeu, Fanny Lauw, J. Perry Hall, Glen N Barber, Ricardo T. Gazzinelli, Katherine A. Fitzgerald, Douglas T. Golenbock

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)194-207
Number of pages14
JournalImmunity
Volume35
Issue number2
DOIs
StatePublished - Aug 26 2011

Fingerprint

Nucleotide Motifs
Toll-Like Receptor 9
Plasmodium falciparum
Genome
DNA
Interferon alpha-beta Receptor
RNA Polymerase III
Cerebral Malaria
Interferon Type I
Falciparum Malaria
Oligonucleotides
Malaria
Parasites
Phosphotransferases
Erythrocytes
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Sharma, S., DeOliveira, R. B., Kalantari, P., Parroche, P., Goutagny, N., Jiang, Z., ... Golenbock, D. T. (2011). Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome. Immunity, 35(2), 194-207. https://doi.org/10.1016/j.immuni.2011.05.016

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.

In: Immunity, Vol. 35, No. 2, 26.08.2011, p. 194-207.

Research output: Contribution to journalArticle

Sharma, S, DeOliveira, RB, Kalantari, P, Parroche, P, Goutagny, N, Jiang, Z, Chan, J, Bartholomeu, DC, Lauw, F, Hall, JP, Barber, GN, Gazzinelli, RT, Fitzgerald, KA & Golenbock, DT 2011, 'Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome', Immunity, vol. 35, no. 2, pp. 194-207. https://doi.org/10.1016/j.immuni.2011.05.016
Sharma S, DeOliveira RB, Kalantari P, Parroche P, Goutagny N, Jiang Z et al. Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome. Immunity. 2011 Aug 26;35(2):194-207. https://doi.org/10.1016/j.immuni.2011.05.016
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. / Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome. In: Immunity. 2011 ; Vol. 35, No. 2. pp. 194-207.
@article{41bd9c2a475d448485596113800bfcb7,
title = "Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome",
abstract = "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.",
author = "Shruti Sharma and DeOliveira, {Rosane B.} and Parisa Kalantari and Peggy Parroche and Nadege Goutagny and Zhaozhao Jiang and Jennie Chan and Bartholomeu, {Daniella C.} and Fanny Lauw and Hall, {J. Perry} and Barber, {Glen N} and Gazzinelli, {Ricardo T.} and Fitzgerald, {Katherine A.} and Golenbock, {Douglas T.}",
year = "2011",
month = "8",
day = "26",
doi = "10.1016/j.immuni.2011.05.016",
language = "English",
volume = "35",
pages = "194--207",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome

AU - Sharma, Shruti

AU - DeOliveira, Rosane B.

AU - Kalantari, Parisa

AU - Parroche, Peggy

AU - Goutagny, Nadege

AU - Jiang, Zhaozhao

AU - Chan, Jennie

AU - Bartholomeu, Daniella C.

AU - Lauw, Fanny

AU - Hall, J. Perry

AU - Barber, Glen N

AU - Gazzinelli, Ricardo T.

AU - Fitzgerald, Katherine A.

AU - Golenbock, Douglas T.

PY - 2011/8/26

Y1 - 2011/8/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80051880722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051880722&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2011.05.016

DO - 10.1016/j.immuni.2011.05.016

M3 - Article

VL - 35

SP - 194

EP - 207

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -