Social amoebae trap and kill bacteria by casting DNA nets.

Area of Science:

• Evolutionary biology
• Cellular and molecular immunology
• Microbiology

Background:

• Neutrophil extracellular traps (NETs) are DNA nets with antimicrobial properties crucial for host defense.
• The evolutionary origins of NETs and similar DNA-based defense mechanisms remain largely unknown.
• Understanding the evolutionary history of innate immunity provides insights into host-pathogen interactions.

Purpose of the Study:

• To investigate the presence and function of extracellular traps (ETs) in the social amoeba Dictyostelium discoideum.
• To explore the evolutionary history of DNA-based host defense mechanisms.
• To identify the molecular components involved in ET production in D. discoideum.

Main Methods:

• Stimulation of Dictyostelium discoideum Sentinel cells with bacteria and lipopolysaccharide.
• Investigating the role of reactive oxygen species (ROS) in ET production.
• Gene disruption of Toll/Interleukin-1 receptor domain-containing protein TirA and NADPH oxidases.
• Assessing bacterial clearance in genetically modified D. discoideum.

Main Results:

• Dictyostelium discoideum Sentinel cells produce ETs in response to bacterial and lipopolysaccharide stimuli.
• ET production is dependent on reactive oxygen species (ROS) and requires the TirA protein and NADPH oxidases.
• Disruption of genes involved in ET production led to reduced bacterial clearance.
• D. discoideum serves as a model for studying conserved mechanisms of cell-intrinsic immunity.

Conclusions:

• Extracellular trap (ET) formation is an ancient innate immune defense mechanism predating the emergence of metazoans.
• Dictyostelium discoideum provides a valuable model for studying the evolution and conservation of DNA-based immunity.
• The findings suggest a deep evolutionary origin for DNA-based host defense strategies.