A study published in Nature Communications from researchers at the University of Geneva and Baylor College of Medicine show the amoeba Dictyostelium discoideum uses antimicrobial defense systems akin to phagocytes of the human innate immune system, and it evolved these defenses much earlier than initially thought.
D. discoideum is a soil living amoeba often referred to as “slime mold”. These social amoebas tend to aggregate together, particularly during times of low resources, to form a mobile “slug” composed of ~100,000 individual amoebas. The slug’s role is to disperse spores on the wind to seed new areas containing better resources. Within this slug, 80% of the amoeba will become spores, while approximately 20% will sacrifice themselves to form a stalk, a primitive spore dispersal method. About 1% of the amoeba though takes on defense duties by protecting the stalk/spore dispersion mechanism from invading bacteria.
It is this 1% that the researchers were interested in. Termed “sentinel cells”, these specialized amoebas use antimicrobial defense systems extremely similar to those used by phagocytes within the human innate immune system. The sentinel cells use either reactive oxygen species or extracellular traps (ETs) to kill the bacteria.
If the invading microbes are small enough they are ingested by the sentinel cells and subjected to reactive oxygen species (ROS), powerful oxygen-derived chemicals that lyse and kill the bacteria. After stimulation with bacteria or lipopolysaccharide (a bacterial cell wall component), the researchers showed this mechanism to be dependent on the enzyme NOX2, which develops bleach, ozone, and other free radicals from unreactive precursors. This process is identical to the phagocytosis process used by lymphocytes in the human system to eliminate invading pathogens.
If the microbes are too large to be phagocytosed, the sentinel cells release ETs. These traps contain DNA and antimicrobial granules, and the release is dependent on Toll/Interleukin-1 receptor domain-containing protein (TirA) and ROS-generating NADPH oxidases within the sentinel cells; when these genes are knocked out the slug is overcome by bacteria. It was initially thought ETs evolved with metazoans, but as D. discoideum evolved first this discovery proves that this part of our innate immunity evolved even farther in the past.
Of clinical importance, “[o]ur results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity,” wrote study coauthor Thierry Soldati of the University of Geneva in a press release. Identifying the stimulatory processes behind sentinel cell antimicrobial resistance could help researchers harness our innate immune system to fight off pervasive invaders such as MRSA, CRE, and even cancer.
Edward Marks is a PhD student at the University of Delaware. His research involves the healing of myocardial tissue after major cardiac events using nanomedicine techniques, with the goal of pushing any advancement directly into the clinic. Edward received his BS from Rutgers University and Masters from the University of Delaware.
