Abstract

Human cells possess intricate nucleic acid recognition processes for monitoring cellular stress and pathogen infection, which trigger the production and release of interferons and cytokines to alert neighboring cells including cells of the immune system. Various classes of nucleic acid sensors, each specific to detecting modified or unmodified, structured or unstructured DNA or RNA, have been identified and are characterized by distinct subcellular localization and also cell-type-specific expression patterns. These sensors include various nucleotidyl transferases producing second messenger small ribonucleic nucleic acid molecules as well as membrane-bound receptors ultimately leading to phosphorylation of transcription factors driving cytokine and interferon expression. This meeting focuses on cytoplasmic DNA and RNA sensors and the function of their linear and circular oligonucleotide second messenger cGAMP and 2’,5’-oligoadenylate produced upon activation. Substantial progress has been made in identification of the structures of these sensors, their nucleic acid ligands and second messenger molecules, as well as the underlying molecular pathways leading to transcriptional activation. Animal models inactivating various pathways of innate immunity have been developed. This progress has enabled targeted development of antagonists and agonists of cytokine and interferon production for therapeutic targeting of inflammatory diseases and vaccine adjuvant development, respectively. An international group of academic and industry scientists and clinicians with expertise in biochemistry and structural biology, nucleic acid chemistry, immunology, human genetics, virology, rheumatology and vaccine development will converge at this meeting to discuss the latest developments in this field.