Innate immune receptors include a plethora of membrane-associated proteins as well as intracellular receptors that directly bind or sense the presence of pathogen-associated molecular patterns (PAMPs). The importance of innate immune receptors was first appreciated in infectious diseases and autoinflammatory disorders, but it is now clear that their roles extend beyond innate immunology. The crucial roles of these receptors in many clinically relevant fields, and their newly documented role in non-immune cells, underscore their importance in biologic processes and diseases. This conference will address the ligands and signaling mechanisms of a diverse set of innate immune receptors as well as the profound impacts of innate immune receptors on the microbiome, which in turn has impacts on multiple organ systems. The program includes discussion of the intrinsic functions of innate immune receptors within adaptive immune cells, non-immune cells such as epithelial and endothelial cells, and their roles in cancer and stem cells. The pleitrophic effects of this important receptor class have far-reaching consequences for critical biological processes such as cancer cell death and signaling, DNA damage, stress response, stem cell proliferation/differentiation, vaccine adjuvanticity, age-related dementia, metabolic disorders and microbiome balance. By the nature of the topic, this conference brings together an interdisciplinary group of investigators to catalyze cross-fertilization of ideas and stimulate important medical advances.