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.