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

Kislay Parvatiyar, Zhiqiang Zhang, Rosane M. Teles, Songying Ouyang, Yan Jiang, Shankar S. Iyer, Shivam A. Zaver, Mirjam Schenk, Shang Zeng, Wenwan Zhong, Zhi Jie Liu, Robert L. Modlin, Yong Jun Liu, Genhong Cheng

Research output: Contribution to journalArticlepeer-review

273 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1155-1161
Number of pages7
JournalNature immunology
Volume13
Issue number12
DOIs
StatePublished - Dec 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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