Host immune sensing of cyclic dinucleotides during bacterial infection.
The innate immune system is comprised of germ-line encoded receptors that detect components of microbes. Cyclic dinucleotides have emerged as potent modulators of host inflammation and immunity. During cytosolic infiltration by bacterial pathogens, binding of bacterial cyclic dinucleotides to the host receptor STING results in the activation of a host interferon response. Additionally, during viral infection or cellular damage, cytosolic DNA is sensed by the host protein cGAS, resulting in production of cyclic AMP-GMP (cGAMP) which also results in STING activation. We recently identified a novel cyclic dinucleotide binding protein RECON, which regulates host inflammation through NF-kB signaling specifically in response to bacterial nucleotides. Activation of these pathways has been implicated in host resistance to infection as well as autoinflammatory disorders. We are currently detailing the role of cyclic dinucleotide immune detection and its impacts on host signal transduction and infection outcome using tissue culture and murine models of infection.
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