Abstract
There are at least five families of microbe-detection receptors that function to detect and eradicate potentially infectious microorganisms that enter multicellular eukaryotes. While a multitude of proteins regulating innate immune signal transduction have already been defined, continuous genetic screening for regulators of innate immunity may not yield as significant insight into the operation of these pathways as was obtained in the past. This diminished return on experimental investment suggests that we are approaching the asymptote of genetics-only approaches to study innate immunity. In contrast, it remains unclear how known regulators of innate immunity interact within the infrastructure of mammalian cells to execute their signaling functions. In this Perspective, I first highlight the locations within mammalian cells that permit innate immune signal transduction and then offer a model whereby structurally distinct proteins can be grouped functionally through their ability to assemble platforms of regulators on the signaling organelles of the innate immune system.