Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4
AuthorsAndrade, Warrison A.
Shaffer, Scott A.
Dillard, Joseph P.
Fitzgerald, Katherine A.
Kurt-Jones, Evelyn A.
Golenbock, Douglas T.
UMass Chan AffiliationsProteomics and Mass Spectrometry Facility
Department of Biochemistry and Molecular Pharmacology
Program in Innate Immunity
Department of Medicine, Division of Infectious Diseases and Immunology
type I interferon
Bacterial Infections and Mycoses
Immunology of Infectious Disease
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AbstractThe 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.
SourceCell 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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39999
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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/).
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>