Social amoebae trap and kill bacteria by casting DNA nets

Abstract

Extracellular traps (ETs) from neutrophils are reticulated nets of DNA decorated with anti-microbial granules, and are capable of trapping and killing extracellular pathogens. Various phagocytes of mammals and invertebrates produce ETs, however, the evolutionary history of this DNA-based host defence strategy is unclear. Here we report that Sentinel (S) cells of the multicellular slug stage of the social amoeba Dictyostelium discoideum produce ETs upon stimulation with bacteria or lipopolysaccharide in a reactive oxygen species-dependent manner. The production of ETs by S cells requires a Toll/Interleukin-1 receptor domain-containing protein TirA and reactive oxygen species-generating NADPH oxidases. Disruption of these genes results in decreased clearance of bacterial infections. Our results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity, and suggest that the origin of DNA-based ETs as an innate immune defence predates the emergence of metazoans.

Evolution of Cell-Autonomous Effector Mechanisms in Macrophages versus Non-Immune Cells

“…During the multicellular slug-stage, the selective pressure to avoid parasitic exploitation is increased (33). Remarkably, this pressure appears to have driven a subgroup of these amoebae, termed sentinel cells (S-cells), to develop immune-like functions complete with Toll/Interleukin-1 receptor domain signaling pathways (34) and the ability to deploy extracellular DNA nets (or traps) that can sequester and kill bacteria (35). Thus, amoebae enlist both offensive and defensive effector mechanisms that are conserved throughout the evolution of mammals, implying that the ability to kill bacteria, either as a food source or for self-defense, emerged well before the appearance of metazoans.…”

Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium

“…It is plausible that the genotoxin might be an integral bacterial part that is not inactivated by heat sterilization, or it could be a substance generated as a consequence of ‘digesting’ this food source. Another intriguing possibility comes from the resemblance of Dictyostelium to neutrophils, which kill ingested bacteria by using respiratory burst activity (Chen et al, 2007; Cosson and Soldati, 2008; Zhang et al, 2016). Neutrophil killing generates a battery of reactive molecules such as hypochlorus acid and reactive oxygen species, which are known to be highly mutagenic (Knaapen et al, 2006).…”

Lipopolysaccharide Detection across the Kingdoms of Life

“…However, while these responses are mediated by TLRs in mammals, no TLRs are present in the genome of D. discoideum . Interestingly, D. discoideum produce a protein called TirA, which is necessary for LPS-induced antibacterial responses in this organism [65, 66]. TirA may have some relation to mammalian TLRs, as it contains a TIR domain.…”