UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity; Department of Biochemistry and Molecular Pharmacology; Proteomics and Mass Spectrometry Facility

Date

6-14-2016

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Bacteriology | Immunity | Immunology of Infectious Disease

Abstract

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that complete IFN-beta induction by live GC depends on both cGAS and TLR4. Type I IFN is detrimental to the host, and dysregulation of iron homeostasis genes may explain lower bacteria survival in cGAS(-/-) and TLR4(-/-) cells. Collectively, these observations reveal cooperation between TLRs and cGAS in immunity to GC infection.

Rights and Permissions

Citation: Cell Rep. 2016 Jun 14;15(11):2438-48. doi: 10.1016/j.celrep.2016.05.030. Epub 2016 Jun 2. Link to article on publisher's site

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2016.05.030

Related Resources

Link to Article in PubMed

Keywords

Neisseria gonorrhoeae, STING, TLR4, cGAS, type I interferon

Journal Title

Cell reports

PubMed ID

27264171

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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