Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4
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Authors
Andrade, Warrison A.Agarwal, Sarika
Mo, Shunyan
Shaffer, Scott A.
Dillard, Joseph P.
Schmidt, Tobias
Hornung, Veit
Fitzgerald, Katherine A.
Kurt-Jones, Evelyn A.
Golenbock, Douglas T.
UMass Chan Affiliations
Proteomics and Mass Spectrometry FacilityDepartment of Biochemistry and Molecular Pharmacology
Program in Innate Immunity
Department of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2016-06-14Keywords
Neisseria gonorrhoeaeSTING
TLR4
cGAS
type I interferon
Bacterial Infections and Mycoses
Bacteriology
Immunity
Immunology of Infectious Disease
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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.Source
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 siteDOI
10.1016/j.celrep.2016.05.030Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39999PubMed ID
27264171Related Resources
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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/).
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http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2016.05.030
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Except where otherwise noted, this item's license is described as <p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</p>