Inflammation associated altered nucleic acid levels and localization

Abstract

The innate immune response in mammalian cells is a primary defense mechanism against pathogen invasions. The activation of highly sensitive sensors called pattern recognition receptors (PRRs) precedes the initiation of the innate immune response pathway. The PRRs detect pathogen or danger-associated molecular signatures. A subset of PRRs recognizes nucleic acids and signals the Type-I IFN response pathway, leading to the upregulation of inflammatory cytokines. This study investigates the effect of introducing DNA vectors and other nucleic acids in mammalian cells on the Type-I IFN response pathway and the activation of an antiviral pathway mediated by RNase L. We report the formation of nucleic acid assemblies within cells upon introducing nucleic acids. These assemblies contain DNA and are rich in RNA, and have not been previously described. Our findings demonstrate that the introduction of nucleic acids upregulates Type-I IFN genes and enhances RNase L levels, providing insight into the mechanism of nucleic acid-mediated immune responses.