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Cytosolic DNA sensing via the stimulator of interferon genes adaptor: Yin and Yang of immune responses to DNA

Lookup NU author(s): Dr Henrique De Paula Lemos, Dr Lei Huang, Professor Andrew Mellor

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Abstract

DNA is immunogenic and many cells express cytosolic DNA sensors that activate the stimulator of interferon genes (STING) adaptor to trigger interferon type I (IFN-β) release, a potent immune activator. DNA sensing to induce IFN-β triggers host immunity to pathogens but constitutive DNA sensing can induce sustained IFN-β release that incites autoimmunity. Here, we focus on cytosolic DNA sensing via the STING/IFN-β pathway that regulates immune responses. Recent studies reveal that cytosolic DNA sensing via the STING/IFN-β pathway induces indoleamine 2,3 dioxygenase (IDO), which catabolizes tryptophan to suppress effector and helper T-cell responses and activate Foxp3-lineage CD4(+) regulatory T (Treg) cells. During homeostasis, and in some inflammatory settings, specialized innate immune cells in the spleen and lymph nodes may ingest and sense cytosolic DNA to reinforce tolerance that prevents autoimmunity. However, malignancies and pathogens may exploit DNA-induced regulatory responses to suppress natural and vaccine-induced immunity to malignant and infected cells. In this review, we discuss the biologic significance of regulatory responses to DNA and novel approaches to exploit DNA-induced immune responses for therapeutic benefit. The ability of DNA to drive tolerogenic or immunogenic responses highlights the need to evaluate immune responses to DNA in physiologic settings relevant to disease progression or therapy.


Publication metadata

Author(s): Lemos H, Huang L, McGaha TL, Mellor AL

Publication type: Review

Publication status: Published

Journal: European Journal of Immunology

Year: 2014

Volume: 44

Issue: 10

Pages: 2847-2853

Print publication date: 03/10/2014

Online publication date: 25/08/2014

Acceptance date: 29/07/2014

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

URL: http://dx.doi.org/10.1002/eji.201344407

DOI: 10.1002/eji.201344407

PubMed id: 25143264


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