Sensing from within: how the immune system discriminates friend from foe
Established in 1950 in honor of former NIH director Dr. Rolla E. Dyer, a noted authority on infectious diseases. The lectureship, part of the NIH Director’s Wednesday Afternoon Lecture Series, features internationally renowned researchers who have contributed substantially to medical as well as biological knowledge of infectious diseases. The central goal of Dr. Fitzgerald’s research is understanding the molecular mechanisms controlling the inflammatory response and defining how the immune system discriminates between pathogens and host molecules to avoid damaging inflammatory diseases. Our health relies on the ability of the immune system to mount timely and selective responses to dangerous microbes. For example, the immune system must respond aggressively to pathogens yet avoid responding to harmless commensals that line our skin and mucosal surfaces. While we have learned a lot about the receptors that recognize microbial products, the central question in immunity remains: How does the immune system discriminate friend from foe? A central theme that has emerged from Dr. Fitzgerald’s work over the last decade is that nucleic acids represent a primary means of alerting the immune system to the presence of pathogens. But beneficial commensals and our own cells contain nucleic acids, too. She believes that the location of nucleic acids allows the immune system to discriminate friend from foe. Accumulation of nucleic acids in cytosolic compartments is perceived as a danger signal during infection. Pathogens frequently infiltrate the cytosolic compartment to establish infection and evade extracellular defenses. Once inside, nucleic acids from the pathogens’ genomes or from their replicative process activate cytosolic sensors. Mis-localization of our own nucleic acids can also drive inflammation (e.g. in autoimmune diseases such as lupus). Dr. Fitzgerald’s laboratory has made a number of important and unique contributions to these areas. Her lab has defined nucleic acids as microbial triggers during infection with viruses, bacteria, and parasites, and identified new receptors for these nucleic acids and new regulation of the pathways induced. For her lecture, Dr. Fitzgerald will describe how nucleic-acid-sensing pathways drive host-defense and the inflammatory process. Recently, human patients harboring mutations in components of these pathways have been identified. Using murine models, the lab has been exploring how the mutations lead to inflammatory disease. Further, Dr. Fitzgerald will also describe some of her lab’s work demonstrating how long non-coding RNAs regulate the inflammatory response.
Long > 60 min