Innate Immunity: Complement and Beyond

摘要

ABSTRACT Support is requested for a Keystone Symposia conference entitled Innate Immunity: Complement and Beyond organized by Drs. Claudia Kemper, Christoph Binder and Feng Shao. The conference will be held in Snowbird, Utah from April 3-6, 2022. Innate immunity is a pillar of the host’s defense against infection and noxious self. Pathogen or danger recognition systems (PRRs) including toll-like receptors (TLRs), inflammasomes, and retinoic acid-inducible gene I (RIG-I) like receptors are broadly recognized as central nodes of innate immune responses and have been staples of immunity research. The complement system, however, generally evokes much less enthusiasm in research, despite being the oldest PRR from an evolutionary perspective. Yet, this view is changing; while the complement system was once viewed as a mere lytic pathogen-killer, it is now recognized as an active intracellular orchestrator of normal cell physiology. This, together with the realization that an increasing number of human diseases, even COVID-19, involve complement perturbations, has spurred a reinvigorated interest in complement biology and its therapeutic targeting. However, our knowledge of how complement exerts non-canonical activities and how it intersects with other PRRs is sparse. This Keystone Symposia conference will provide a timely account of recent paradigm shifts in our understanding of complement/PRR-instructed immunity with a specific eye on emerging roles in basic cellular processes including regulation of chromatin structure, metabolism, cell death, clearance of cellular debris/corpses, and maintenance of normal CNS function. A second focus is on exploring how aberrant function of these new PRR activities contribute to infection and autoimmunity but also to less intuitive clinical conditions like changes in cognition and behavior. This holistic and ‘complement-inclusive’ vantage-point on PRR biology brings together interdisciplinary investigators from academia and industry for cross-fertilization of novel ideas and collaborations towards biomedical progress in harnessing complement to combat human disease.