STING regulates intracellular DNA-mediated, type i interferon-dependent innate immunity

Hiroki Ishikawa, Zhe Ma, Glen N Barber

Research output: Contribution to journalArticle

1013 Citations (Scopus)

Abstract

The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defence countermeasures, which include the production of type I interferon (IFN). However, little is known about how the innate immune system is galvanized to respond to DNA-based microbes. Here we show that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection. Murine embryonic fibroblasts, as well as antigen presenting cells such as macrophages and dendritic cells (exposed to intracellular B-form DNA, the DNA virus herpes simplex virus 1 (HSV-1) or bacteria Listeria monocytogenes), were found to require STING to initiate effective IFN production. Accordingly, Sting-knockout mice were susceptible to lethal infection after exposure to HSV-1. The importance of STING in facilitating DNA-mediated innate immune responses was further evident because cytotoxic T-cell responses induced by plasmid DNA vaccination were reduced in Sting-deficient animals. In the presence of intracellular DNA, STING relocalized with TANK-binding kinase 1 (TBK1) from the endoplasmic reticulum to perinuclear vesicles containing the exocyst component Sec5 (also known as EXOC2). Collectively, our studies indicate that STING is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.

Original languageEnglish
Pages (from-to)788-792
Number of pages5
JournalNature
Volume461
Issue number7265
DOIs
StatePublished - Oct 8 2009

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Innate Immunity
Interferons
DNA
Human Herpesvirus 1
Genes
Bites and Stings
Immune System
B-Form DNA
Interferon Type I
DNA Vaccines
DNA Viruses
Essential Genes
Listeria monocytogenes
Antigen-Presenting Cells
Infection
Knockout Mice
Endoplasmic Reticulum
Dendritic Cells
Vaccination
Plasmids

ASJC Scopus subject areas

  • General

Cite this

STING regulates intracellular DNA-mediated, type i interferon-dependent innate immunity. / Ishikawa, Hiroki; Ma, Zhe; Barber, Glen N.

In: Nature, Vol. 461, No. 7265, 08.10.2009, p. 788-792.

Research output: Contribution to journalArticle

Ishikawa, Hiroki ; Ma, Zhe ; Barber, Glen N. / STING regulates intracellular DNA-mediated, type i interferon-dependent innate immunity. In: Nature. 2009 ; Vol. 461, No. 7265. pp. 788-792.
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