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SP0049 Dna aggregates as alarmins
  1. D Pisetsky
  1. Medicine, Duke University Medical Center, Durham, North Carolina, United States

Abstract

DNA is a large polymeric molecule that displays powerful immunological activities and operates in the context of multi-component aggregates to alarm the immune system and stimulate innate immunity. Although DNA has important roles in normal host defense, DNA can serve as an autoantigen and autoimmunogen by itself or in association with other immunologically active nuclear molecules. In the setting of systemic lupus erythematosus (SLE), DNA is a key target antigen; while antibodies to pure DNA double stranded DNA serve as important biomarkers, the relevant antigenic form of DNA during disease is the nucleosome in which DNA is bound to histones. Furthermore, nucleosomes can be components of microparticles which are small membrane-bound structures that are released from dead and dying cells. MPs can stimulate immune responses and serve as a nidus for immune complex formation. In normal immunity, DNA can interact with nucleic acid sensors in the cytoplasm of cells to stimulate responses including production of type 1 interferon. These sensors respond to DNA from intracellular organisms such as bacteria and viruses although damaged DNA and DNA from mitochondria can also interact with these receptors. While these sensors are intracellular, they can interact with extracellular DNA that is introduced or transfected into the cell; this translocation event occurs with DNA bound with other molecules. In another facet of host defense, DNA can be released from neutrophils during a process termed NETosis. A NET or neutrophil extracellular trap is a mesh-like structure comprised of DNA as well as granule proteins that have antibacterial activity. NETs can trap and kill bacteria. Thus, in its diverse immunological roles, DNA interacts with other molecules to form aggregates or sub-cellular structures that alarm the immune system, promote host defense or drive critical events in autoimmunity.

Disclosure of Interest None declared

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