DOI: 10.1073/pnas.1006539107. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

10.1073/pnas.1006539107

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Toll-like receptor 9 (TLR9) senses microbial DNA and triggers type I IFN responses in plasmacytoid dendritic cells (pDCs). Previous studies suggest the presence of myeloid differentiation primary response gene 88 (MyD88)-dependent DNA sensors other than TLR9 in pDCs. Using MS, we investigated C-phosphate-G (CpG)-binding proteins from human pDCs, pDC-cell lines, and interferon regulatory factor 7 (IRF7)-expressing B-cell lines. CpG-A selectively bound the aspartate-glutamate-any amino acid-aspartate/histidine (DExD/H)-box helicase 36 (DHX36), whereas CpG-B selectively bound DExD/H-box helicase 9 (DHX9). Although the aspartate-glutamate-alanine-histidine box motif (DEAH) domain of DHX36 was essential for CpG-A binding, the domain of unknown function 1605 (DUF1605 domain) of DHX9 was required for CpG-B binding. DHX36 is associated with IFN-α production and IRF7 nuclear translocation in response to CpG-A, but DHX9 is important for TNF-α and IL-6 production and NF-κB activation in response to CpG-B. Knocking down DHX9 or DHX36 significantly reduced the cytokine responses of pDCs to a DNA virus but had no effect on the cytokine responses to an RNA virus. We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.

Bibliography

Kim, T., Pazhoor, S., Bao, M., Zhang, Z., Hanabuchi, S., Facchinetti, V., Bover, L., Plumas, J., Chaperot, L., Qin, J., & Liu, Y.-J. (2010). Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proceedings of the National Academy of Sciences, 107(34), 15181â15186.

Authors 11

Taeil Kim (first)
Shwetha Pazhoor (additional)
Musheng Bao (additional)
Zhiqiang Zhang (additional)
Shino Hanabuchi (additional)
Valeria Facchinetti (additional)
Laura Bover (additional)
Joel Plumas (additional)
Laurence Chaperot (additional)
Jun Qin (additional)
Yong-Jun Liu (additional)

References 36 Referenced 277

Dates

Type	When
Created	15 years ago (Aug. 9, 2010, 11:08 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:47 p.m.)
Indexed	1 month ago (Aug. 2, 2025, 12:30 a.m.)
Issued	15 years ago (Aug. 9, 2010)
Published	15 years ago (Aug. 9, 2010)
Published Online	15 years ago (Aug. 9, 2010)
Published Print	15 years ago (Aug. 24, 2010)

Funders 0

None

BibTeX

@article{Kim_2010, title={Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells}, volume={107}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1006539107}, DOI={10.1073/pnas.1006539107}, number={34}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kim, Taeil and Pazhoor, Shwetha and Bao, Musheng and Zhang, Zhiqiang and Hanabuchi, Shino and Facchinetti, Valeria and Bover, Laura and Plumas, Joel and Chaperot, Laurence and Qin, Jun and Liu, Yong-Jun}, year={2010}, month=aug, pages={15181–15186} }

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  "abstract": "<jats:p>Toll-like receptor 9 (TLR9) senses microbial DNA and triggers type I IFN responses in plasmacytoid dendritic cells (pDCs). Previous studies suggest the presence of myeloid differentiation primary response gene 88 (MyD88)-dependent DNA sensors other than TLR9 in pDCs. Using MS, we investigated C-phosphate-G (CpG)-binding proteins from human pDCs, pDC-cell lines, and interferon regulatory factor 7 (IRF7)-expressing B-cell lines. CpG-A selectively bound the aspartate-glutamate-any amino acid-aspartate/histidine (DExD/H)-box helicase 36 (DHX36), whereas CpG-B selectively bound DExD/H-box helicase 9 (DHX9). Although the aspartate-glutamate-alanine-histidine box motif (DEAH) domain of DHX36 was essential for CpG-A binding, the domain of unknown function 1605 (DUF1605 domain) of DHX9 was required for CpG-B binding. DHX36 is associated with IFN-\u03b1 production and IRF7 nuclear translocation in response to CpG-A, but DHX9 is important for TNF-\u03b1 and IL-6 production and NF-\u03baB activation in response to CpG-B. Knocking down DHX9 or DHX36 significantly reduced the cytokine responses of pDCs to a DNA virus but had no effect on the cytokine responses to an RNA virus. We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.</jats:p>",
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