Allorecognition and Innate Immunity in the Dictyostelid Social Amoebae

Abstract

Dictyostelid social amoebae such as Dictyostelium discoideum are facultative multicellular organisms that display a number of immune functions commonly found in animals. In the vegetative growth phase, solitary amoebae track and consume food bacteria that occur in their soil environment, and are also susceptible to intracellular bacterial pathogens including those that infect humans. Individual amoebae recognize microbe-associated molecular patterns (MAMPs) to distinguish between bacterial species and adjust their physiology to optimize feeding, but it is during multicellular development that this has been most clearly demonstrated. Starved D. discoideum amoebae aggregate to form mounds, migrating slugs, and spore-filled fruiting bodies in a stereotypical and regulated developmental process. Cell cooperation during multicellular development is maintained by an allorecognition system that ensures the benefits of this group survival mechanism accrues to genetically related amoebae. Allorecognition is accomplished through a cell surface receptor–ligand pair comprised of immunoglobulin (Ig)-repeat ectodomains, and signaling through the receptor acts as a checkpoint for the transition from unicellular to multicellular life. During development, D. discoideum produces innate immune cells capable of clearing interstitial bacteria from migrating slugs and some isolates also harbor specific bacterial species as beneficial endosymbionts. The innate immune cells, when stimulated by bacteria or bacterial lipopolysaccharide, kill bacteria by producing extracellular DNA-based antimicrobial nets or extracellular traps (ETs). As with human innate immune cells, ET production requires reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and Toll/interleukin-1 receptor (TIR) domain-based signaling that triggers ET release. The Dictyostelid social amoebae are part of the monophyletic clade of the Amoebozoa that have achieved multicellularity, so they provide useful comparisons to other species of the Unikont supergroup that highlight the evolutionary pressures that shaped extant immune systems over the past billion years.