The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response.

Parvatiyar, Kislay; Zhang, Zhiqiang; Teles, Rosane M; Ouyang, Songying; Jiang, Yan; Iyer, Shankar S; Zaver, Shivam A; Schenk, Mirjam; Zeng, Shang; Zhong, Wenwan; Liu, Zhi-Jie; Modlin, Robert L; Liu, Yong-jun; Cheng, Genhong (2012). The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response. Nature immunology, 13(12), pp. 1155-1161. Nature Publishing Group 10.1038/ni.2460

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The induction of type I interferons by the bacterial secondary messengers cyclic di-GMP (c-di-GMP) or cyclic di-AMP (c-di-AMP) is dependent on a signaling axis that involves the adaptor STING, the kinase TBK1 and the transcription factor IRF3. Here we identified the heliase DDX41 as a pattern-recognition receptor (PRR) that sensed both c-di-GMP and c-di-AMP. DDX41 specifically and directly interacted with c-di-GMP. Knockdown of DDX41 via short hairpin RNA in mouse or human cells inhibited the induction of genes encoding molecules involved in the innate immune response and resulted in defective activation of STING, TBK1 and IRF3 in response to c-di-GMP or c-di-AMP. Our results suggest a mechanism whereby c-di-GMP and c-di-AMP are detected by DDX41, which forms a complex with STING to signal to TBK1-IRF3 and activate the interferon response.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Schenk, Mirjam

ISSN:

1529-2908

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Mirjam Schenk

Date Deposited:

25 Jul 2017 15:24

Last Modified:

25 Jul 2017 15:24

Publisher DOI:

10.1038/ni.2460

PubMed ID:

23142775

BORIS DOI:

10.7892/boris.102301

URI:

https://boris.unibe.ch/id/eprint/102301

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