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Full-Text Articles in Bacterial Infections and Mycoses
Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock
Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock
Katherine A. Fitzgerald
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 …
Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli
Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli
Katherine A. Fitzgerald
Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1beta. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1beta upon a second …