Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity; Department of Biochemistry and Molecular Pharmacology; Proteomics and Mass Spectrometry Facility
Bacterial Infections and Mycoses | Bacteriology | Immunity | Immunology of Infectious Disease
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.
Neisseria gonorrhoeae, STING, TLR4, cGAS, type I interferon
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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
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
Andrade, Warrison A.; Agarwal, Sarika; Mo, Shunyan; Shaffer, Scott A.; Dillard, Joseph P.; Schmidt, Tobias; Hornung, Veit; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; and Golenbock, Douglas T., "Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4" (2016). Open Access Articles. 2808.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.